Pediatric Herpes Simplex Virus Infection 

Updated: Feb 27, 2019
Author: J Michael Klatte, MD; Chief Editor: Russell W Steele, MD 

Overview

Practice Essentials

Herpes simplex virus (HSV) infections are ubiquitous and have a wide range of clinical manifestations (see the images below). Beyond the neonatal period, most primary HSV-1 infections occur in infancy and childhood and are transmitted primarily by contact with infected saliva. Primary HSV-2 infections are acquired after onset of sexual activity, and genital herpes infections are among the most common sexually transmitted infections.

Primary herpes simplex virus (HSV) gingivostomatit Primary herpes simplex virus (HSV) gingivostomatitis in an infant is shown. This same patient also had concomitant herpes whitlow as shown in the following image.
Herpes whitlow in an infant. Herpes whitlow in an infant.

See 13 Common-to-Rare Infant Skin Conditions, a Critical Images slideshow, to help identify rashes, birthmarks, and other skin conditions encountered in infants.

Also, see the Herpes Simplex Viruses: Test Your Knowledge slideshow for more information on clinical, histologic, and radiographic imaging findings in HSV-1 and HSV-2.

Signs and symptoms

HSV causes myriad clinical presentations, as follows:

  • Orolabial infection

  • Genital infection

  • Intrauterine and perinatal infection (herpes neonatorum)

  • Central nervous system infection

  • Infection in immunocompromised hosts

  • Other infections: Herpetic whitlow, herpes gladiatorum, keratoconjunctivitis, Mollaret meningitis, erythema multiforme

Clinical features of orolabial HSV infection include the following[1] :

  • Abrupt onset of illness

  • Fever

  • Listlessness or irritability

  • Inability to eat and/or drink

  • Gingivitis (with markedly swollen, erythematous, and occasionally bleeding gums)

  • Increased drooling in infants due to pain on swallowing

  • Vesicular lesions on the tongue, buccal mucosa, and palate with extension, at times, to the lips and face (these may rupture and coalesce to form large, ulcerated areas)

  • Tender submandibular or cervical adenopathy

  • In recurrent cases, a prodrome of pain, burning, tingling, and itching

Clinical features of genital HSV infection may include the following:

  • In first episodes, severe constitutional symptoms (eg, fever, malaise, myalgias[2] )

  • Initial itching and pain, followed by more troublesome signs and symptoms

  • Lesions that evolve from vesicles to pustules to wet ulcers and heal by crusting

  • Painful inguinal lymphadenopathy, dysuria, and vaginal discharge

  • Paresthesias of the legs and perineum

  • Urinary retention

Herpes neonatorum may be categorized as follows[3, 4, 5, 6, 7] :

  • Skin, eye, and mucous membrane (SEM) disease

  • Disseminated infection

  • CNS infection

Clinical features of HSV CNS infection may include the following:

  • Insidious or abrupt onset

  • Headache, altered consciousness, and focal neurologic abnormalities at presentation

  • Symptoms of aseptic meningitis (headache, fever, stiff neck, photophobia)

  • Symptoms of autonomic nervous system dysfunction and transverse myelitis (eg, hyperesthesia or anesthesia of the lower back, perineum, or sacral region)

See Clinical Presentation for more detail.

Diagnosis

Measures for diagnosing HSV infection in children include the following:

  • PCR assay (preferred for CNS infection[8, 9, 10] and possibly valuable for disseminated disease)

  • Isolation of the virus in tissue cultures (most common confirmation method)

  • Histologic analysis of scrapings or punch biopsy specimens

  • Cytologic evaluation via a Tzanck preparation

  • Serologic testing (only for determining past HSV exposure)

  • Lumbar puncture and cerebrospinal fluid analysis

  • Immunofluorescent microscopy

  • Brain biopsy

  • Imaging studies: Computed tomography, magnetic resonance imaging

See Workup for more detail.

Management

Specific medical therapy for pediatric HSV infection involves antiviral medications. For neonates born either vaginally or by Caesarian section to infected mothers, determination of primary vs reactivation disease in the mother is necessary to guide duration of therapy. Antiviral agents used include the following:

  • Oral acyclovir (most common)

  • Oral famciclovir (a prodrug that is converted to penciclovir)

  • Oral valacyclovir (a prodrug that is converted to acyclovir)

  • IV acyclovir (for encephalitis, neonatal disease, severe infection in immunocompromised patients, occasional cases of severe orolabial or genital disease,[11, 12, 13, 14] , and recurrent genital HSV infections)

Inpatient management is often indicated for pediatric patients with HSV infections. Suggested criteria include the following:

  • Many children with severe HSV gingivostomatitis who are dehydrated

  • Neonates with disseminated or CNS disease

  • Older patients with encephalitis who may be very ill at presentation

  • HSV infection in immunocompromised patients

Measures to prevent or minimize transmission of genital HSV infection include the following:

  • Avoid contact with individuals excreting the virus (difficult, because they are often asymptomatic)

  • Start oral antiviral therapy at the first symptom or sign of genital HSV disease

  • Promote condom use

  • Provide appropriate evaluation, counseling, and education

Measures to prevent transmission of HSV to newborns include the following:

  • Reassure women with recurrent disease that risk of neonatal infection is low

  • Perform cesarean delivery if a mother has active lesions during delivery[15]

  • Observe infants delivered vaginally by mothers with active genital herpes. At approximately 24 hours, obtain screening laboratory testing as per American Academy of Pediatrics guidelines (see Guidelines Summary)[16]

  • In pregnant women with symptomatic genital herpes, consider antiviral suppressive treatment initiated at the time of diagnosis

See Treatment and Medication for more detail.

Background

Herpes simplex virus (HSV) is a double-stranded, enveloped, DNA virus. Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) belong to the family Herpesviridae, subfamily Alphaherpesvirinae. Following initial infection, the herpes viruses become latent in the sensory neural ganglia (the trigeminal and/or sacral ganglion in HSV-1 infection[17] and usually the sacral ganglion in HSV-2 infection[18] ). Herpes simplex virus infections are ubiquitous and cause a wide range of infections from isolated mucocutaneous lesions to disseminated infection in all age groups. Neonatal herpes simplex virus disease is associated with high morbidity and mortality.[19] Herpes simplex virus infections are among the few non-HIV viral infections amenable to antiviral therapy. Available antiviral chemotherapy can be used to treat infection, shorten the clinical course, and, in certain circumstances, prevent infection with herpes simplex virus.

Pathophysiology

Infection occurs in a susceptible host following exposure of abraded skin or mucosal surfaces to the virus. After inoculation, the virus travels to the sensory ganglion, where it replicates and establishes latency. Recurrence occurs when the virus subsequently migrates along the peripheral sensory nerve, replicates, and produces a typical local lesion.[20, 21] Lifelong latency and periodic recurrences are hallmarks of herpes simplex virus infection. These reactivations can follow exposure to ultraviolet light, stress, hormonal changes, immunosuppression, and other infection.[22, 23] Histology of skin lesions shows cellular balloon degeneration, condensation of nuclear chromatin, and formation of multinucleated giant cells.[21]

Disseminated infection occurs when the host is unable to control viral replication leading to viremia and multiorgan involvement. It is usually seen in neonates and immunocompromised individuals (and very rarely in immunocompetent hosts). Specific immunologic factors responsible for immunity to herpes simplex virus are not completely understood. Both antibody and cell-mediated immunity influence the severity and frequency of recurrences. Herpes simplex virus is also believed to suppress innate immunity by suppressing the production of interferon-alfa and interferon-beta.[24] Additionally, titers of antibodies that mediate antibody-dependent cellular cytotoxicity inversely correlate with severity of neonatal infection.[25]

Frequency

United States

Herpes simplex virus infections occur throughout the world, with humans serving as the only reservoir. The infection is acquired by intimate mucocutaneous contact between a susceptible host and a symptomatic or asymptomatic host shedding virus during primary infection or reactivation. Because the infection results in lifelong latency, the prevalence in any population is cumulative. An estimated 90% of all people worldwide have one or both viruses.[26]

Beyond the neonatal period, most primary HSV-1 infections occur in infancy and childhood and are transmitted primarily by contact with infected saliva. Primary HSV-2 infections are acquired after onset of sexual activity and genital herpes infections are among the most common sexually transmitted infections (STIs).

The prevalence of herpes simplex virus infections depends on socioeconomic status, age, race, and geographic location. For example, approximately 33% of children from lower socioeconomic backgrounds have serologic evidence of herpes simplex virus disease by age 5 years compared with 20% of middle-class individuals. Greater person-to-person contact in crowded living conditions is believed to account at least in part for the role of socioeconomic status in prevalence, though multiple additional factors may also be responsible.[27] The importance of daycare attendance is likely, but not well studied.

In the United States, HSV-2 seroprevalence increases from about 20-30% in patients aged 15-29 years to 35-60% in patients aged 60 years. This change represents a 30% increase compared with data from 1976-1980. Factors that increase the frequency of HSV-2 infection in older adolescents and adults include gender (more women than men), race (more blacks than whites), marital status (more divorced individuals than single or married individuals), and place of residence (more city residents than suburban residents).[28, 29]

The seroprevalence rate of HSV-2 in pregnant women ranges from 15-30%.[30] Approximately 10% of pregnant women who are HSV-2 seronegative have a sexual partner who is HSV-2 seropositive and are, therefore, at risk of contracting a primary HSV-2 infection during pregnancy. Transmission typically results from contact with an asymptomatic sexual partner with a reported risk of acquisition of approximately 10%.[31, 32] Overall, approximately 2% of women acquire herpes simplex virus during pregnancy.

International

Herpes simplex virus has worldwide distribution. The prevalence of genital herpes in developing countries is 2-74% and varies among countries.[33, 34] In African countries that are experiencing HIV epidemics, HSV-2 infection is highly prevalent (≥70%).[35] Evidence suggests that genital herpes simplex virus infection increases the risk of HIV infection and that persons infected with both viruses are more likely to transmit HIV.[36, 37, 38]

Mortality/Morbidity

Most cases of infection with either HSV-1 or HSV-2 do not result in serious morbidity. Morbidity and mortality associated with herpes simplex virus are discussed in Complications. Mortality associated with herpes simplex virus is primarily associated with perinatal infection, encephalitis, and infection in individuals who are immunocompromised.

At the time of vaginal delivery, the risk of herpes simplex virus transmission from a mother with true primary herpes simplex virus infection to her infant is approximately 50%. Women with primary infections at delivery are 10-30 times more likely than women with a recurrent infection to transmit the virus to their babies.[19] Infants born to mothers with newly acquired infections who do not have primary infections in the presence of preexisting immunity caused by another viral infection (ie, first-episode nonprimary) have a transmission risk of 25-30%.[39]

The neonatal herpes simplex virus infection rate is considered to be less than 2% when the mother has active infection caused by the shedding of herpes simplex virus acquired before pregnancy or during the first half of pregnancy (recurrent infection). Approximately two thirds of women who acquire genital herpes during pregnancy have no symptoms.[31, 40] Of mothers who deliver an infant with herpes simplex virus infection, 60-80% have no evidence of genital herpes simplex virus infection at the time of delivery, have no history of previous genital herpes infection, and have sexual partners without a reported  history of genital HSV infection[41] . Of babies born to mothers with a primary infection near the time of delivery, 30-50% acquire the infection.

Neonatal herpes simplex virus infection is estimated to occur in approximately 1 per 3000 deliveries in the United States. In 2006, a lower incidence of 9.6 cases per 100,000 births was ascertained.[42] Studies have determined that herpes simplex virus infections in neonates and infants are associated with substantial morbidity, mortality, and resource use.[43]

 

Race

Although the risk of herpes simplex virus infection is not related to race, infection rates in the United States vary according to race because of various factors, such as racial and ethnic differences in the prevalence of poverty and low socioeconomic status, access to health care, sexual and health-related behavior, and illicit drug use.

By age 5 years, more than 35% of black children are infected with HSV-1 compared with 18% of white children. Through adolescence, the prevalence of antibodies to HSV-1 in blacks is approximately twice the rate among whites. By comparison, the estimated prevalence of antibodies to HSV-1 in Mexican American teenagers is between that of blacks and whites.[27]  By age 40 years, HSV-1 seroprevalence is similar among blacks and whites. The prevalence of HSV-2 antibodies among blacks is 3-4 times higher than that among whites.

Seroprevalence among women of childbearing age in the late 1970s was estimated to be 50% for blacks and 20% for whites. By the late 1980s, rates of infection had increased to approximately 60% for blacks and 35% for whites. As shown in 2 nationwide surveys of HSV-2 seroprevalence in the last 2 decades, the cumulative lifetime incidence of HSV-2 reaches 25% in white women, 20% in white men, 80% in black women, and 60% in black men.[44] Studies have indicated that the seroprevalence of HSV-2 among Hispanics ranges from 17-22.3%. Infants born to non-Hispanic white women may be at higher risk of herpes simplex virus infections. This is a result of a greater likelihood that these women are herpes simplex virus seronegative and therefore at risk of acquiring a primary HSV-1 or HSV-2 infection in late pregnancy.

Sex

Infection rates with HSV-1 tend to be similar in both genders during early childhood. However, through adolescence, the prevalence of antibodies to HSV-1 is slightly higher among females than among males. Rates of HSV-2 infection are higher in women than in men.[45] Nationwide surveys of HSV-2 seroprevalence over the last 2 decades have demonstrated cumulative lifetime incidences of 25% in white women and 80% in black women. This compares with rates of 20% in white men and 60% in black men.

Age

Beyond the neonatal period, most childhood herpes simplex virus infections are caused by HSV-1. The seroprevalence of HSV-1 antibodies increases with age, and its rate is 20% by age 5 years. Between the ages of 14-19 years, HSV-1 seroprevalence in the general population increases to 35%,[27]  and by 20-40 years of age 40-60% of individuals are likely to be seropositive for HSV-1. As a reflection of the association between infection and sexual activity, many HSV-2 infections occur around puberty and early adolescence, including gingivostomatitis from orogenital contact. A progressive increase in HSV-2 infections occurs in all populations beginning in adolescence.[45] In the United States, HSV-2 seroprevalence increases from approximately 20-30% in those aged 15-29 years to 35-60% in those aged 60 years. Most neonatal infections are caused by HSV-2, but increasing proportions are being caused by HSV-1.[19, 46]

 

 

Presentation

History

Herpes simplex virus (HSV) causes myriad clinical presentations. The course depends on the age of the patient, the immune status of the host, the site of infection, the individual's previous immunity to autologous or heterologous viruses, and the antigenic type of the virus. Herpes simplex virus type 1 (HSV-1) classically causes infection above the waist and the infections are localized to the mouth and oropharynx, whereas herpes simplex virus type 2 (HSV-2) usually causes genital infections and can also cause CNS or disseminated disease in neonates.[47]

Compared with latent infection, primary infection with either virus is frequently associated with systemic signs, increased severity of symptoms, and increased rates of complications. Upon reactivation, both viruses establish latent infections in sensory neurons and can cause recurrent disease at or near the entry site into the body.

Orolabial infection

Primary infection

Most infections are caused by HSV-1 and are localized to the mouth and oropharynx. Only 10-30% of orolabial infections are symptomatic.

The most common clinical presentation of first-episode, primary herpes simplex virus infection in children (usually aged 6 mo to 5 y) is acute herpetic gingivostomatitis, as is shown in the image below.

Primary herpes simplex virus (HSV) gingivostomatit Primary herpes simplex virus (HSV) gingivostomatitis in an infant is shown. This same patient also had concomitant herpes whitlow as shown in the following image.

Clinical features include the following[1] :

  • Abrupt onset of illness

  • Fever

  • Listlessness or irritability

  • Inability to eat and/or drink

  • Gingivitis (with markedly swollen, erythematous, and occasionally bleeding gums)

  • Increased drooling in infants due to pain on swallowing

  • Vesicular lesions on the tongue, buccal mucosa, and palate with extension, at times, to the lips and face (These may rupture and coalesce to form large, ulcerated areas.)

  • Tender submandibular or cervical adenopathy

The lesions can be quite painful and symptoms may persist for 10-14 days. Primary herpes simplex virus infection of the oropharynx may be associated with viral shedding for as long as 23 days.

Primary HSV-1 infection of the oropharynx in adolescents and adults usually manifests as pharyngotonsillitis rather than gingivostomatitis. Patients usually present with fever, malaise, odynophagia, and headache with vesiculoulcerative lesions on the tonsils.

Primary HSV-2 infection can have a presentation similar to this after orogenital contact and it may occur concurrently with genital herpes simplex virus infection.

Reactivation

Reactivation of herpes simplex virus from the trigeminal ganglion may follow oral trauma or dental procedures but is usually asymptomatic.

A mild prodrome of localized pain, tingling, burning, or itching is followed by eruption of vesicular lesions. The prodrome may occur 6-53 hours before the first vesicular lesions appear.

The most common site of recurrent orolabial lesions is the vermilion border. On occasion, vesicles may be noted on other areas of the face or in the nares, often at sites contaminated by infected saliva during the initial infection. The pattern of recurrent disease varies greatly from one person to another. However, specific triggers may be fairly predictable for individual patients and the lesions tend to recur at the same site as the original lesions.

HSV-1 orolabial infections recur at a rate of approximately 0.1 episode per month or 1.2 per year.

Genital infections

Primary infection occurs in the absence of preexisting antibodies to herpes simplex virus, either HSV-1 or HSV-2. First episode nonprimary infections occur in the absence of any previous signs or symptoms of genital herpes but in the presence of preexisting heterologous antibodies. Formerly, HSV-2 accounted for 80-90% of herpes genitalis, however, HSV-1 has been associated with an increasing prevalence of genital outbreaks.[48]  

Primary infection

Primary, symptomatic, first-episode genital infections are characterized by severe constitutional symptoms, including fever, malaise, and myalgias.[2] Itching and pain usually are the initial symptoms, followed in 24-48 hours by more troublesome signs and symptoms.

Lesions evolve from vesicles to pustules to wet ulcers and heal by crusting. New lesions develop over 7-8 days, and are primarily distributed over the labia majora, labia minora, mons pubis, vaginal mucosa, cervix, and on the shaft of the penis. Painful inguinal lymphadenopathy, dysuria, and vaginal discharge are frequent complaints. Complications in both sexes can include paresthesias of the legs and perineum. Urinary retention, more common in women than in men, may be reported. Approximately 85% of women report vaginal discharge, with 25% of men reporting urethral discharge[18] . Mean duration of viral shedding is 12 days.

Preexisting antibodies to HSV-1 have an ameliorating effect on the severity of disease caused by HSV-2. Previous orofacial infection with HSV-1 generally protects a person against genital infection with HSV-1 but not HSV-2.

Most primary genital herpes simplex virus infections are asymptomatic, and 70-80% of seropositive individuals have no history of symptomatic genital herpes. Periodic subclinical recurrences with viral shedding make these individuals sources of infection, however.[49]

Nonprimary first episode infections have lower frequencies of systemic symptoms, fewer lesions and more rapid healing of those lesions than in patients with primary infections, presumably due to preexisting heterologous antibodies.

Reactivation

Recurrences are more common with HSV-2 infections than with HSV-1 infections (5 vs 1 per y). Individuals with HSV-2 infection generally have high rates of recurrence in the first and second years followed by a substantial decrease in subsequent years (median, 2 per y). About 25% of individuals have at least one recurrence in 5 years. Recurrences often follow stressful events, illness, trauma, and menstruation.

Most reactivations are asymptomatic (1% of individuals with previous HSV-2 infection have asymptomatic viral shedding on any given day).[50]

When symptomatic reactivation occurs, genital lesions are typically few. Tender lymphadenopathy, dysuria, vaginal discharge, and systemic symptoms are less common.

Intrauterine and perinatal infections

Congenital herpes simplex virus infection is a very rare entity and has been infrequently reported in the literature.[51, 52] Manifestations can include skin lesions and scars, chorioretinitis, and microcephaly.

Most neonatal herpes simplex virus infections occur at the time of delivery through the genital tract of a woman asymptomatically shedding virus. History of previous infection and presence of maternal antibody are protective, as approximately half of neonates exposed to maternal primary herpes simplex virus infection contract the virus as opposed to less than 5% of those exposed to recurrent herpes simplex virus disease.[19, 3, 4]

Herpes neonatorum can be categorized as follows[3, 4, 5, 6, 7] :

  • Skin, eye, and mucous membrane (SEM) disease: Infection with herpes simplex virus limited to SEM historically accounts for about 20% of all neonatal herpes simplex virus infections. Infants with SEM infections generally present at age 10-12 days. Skin lesions tend to appear at the site of trauma. Many newborns with herpes simplex virus–related SEM disease do not present with symptoms of systemic illness. Outcome of SEM disease is excellent with prompt antiviral therapy; however, without treatment 75% of the cases progress to disseminated disease.

  • Disseminated infection: Disseminated infection now accounts for approximately 25% of herpes simplex virus infections in newborns. The early recognition and prompt treatment of herpes simplex virus–related SEM disease has resulted in lower rates of progression to disseminated disease than in years past. Neonatal HSV infection acquired peripartum and manifesting as disseminated disease will usually present between days 2-12 of life, given a minimum incubation period for HSV infection of 2 days.[4, 41, 53] Disseminated disease manifests as severe infection, often with hepatic, pulmonary, and neurologic dysfunction or failure. In the absence of prompt recognition and early institution of antiviral treatment, disseminated disease has a high mortality rate.

  • CNS infection: Nearly one-third of infants with neonatal herpes simplex virus infection have meningoencephalitis as the sole manifestation of disease. Patients usually present with symptoms and signs of illness at 2-3 weeks of age. Initial manifestations include lethargy, irritability, and focal seizures. Without treatment, most children with CNS disease die and survivors sustain severe neurologic impairment.

Herpes simplex virus CNS infection

Herpes simplex virus is the most common cause of sporadic encephalitis in the United States.[54, 55, 56]  and HSV-1 is the second most commonly identified cause of encephalitis in children (behind only enterovirus encephalitis).[57] One third of all cases of herpes simplex virus encephalitis are believed to occur in the pediatric population.

Herpes simplex virus encephalitis may be a manifestation of primary or recurrent infection with the virus. The infection may have an insidious or an abrupt onset. Patients present with headache, altered consciousness, and focal neurological abnormalities (often consistent with temporal lobe involvement).

Aseptic meningitis caused by herpes simplex virus can occur after primary genital HSV-2 infection. Patients with herpes simplex virus meningitis present with headache, fever, stiff neck, and photophobia. Symptoms usually begin 3-12 days after the onset of genital lesions. They reach maximum severity by 2-4 days into the illness, and gradually diminish over 2-3 days.

Dysfunction of the autonomic nervous system and transverse myelitis has been associated with genital herpes simplex virus infection. Symptoms may include hyperesthesia or anesthesia of the lower back, perineum, or sacral region. Urinary retention and constipation are other associated symptoms.

Infection in immunocompromised hosts

Severe herpes simplex virus infection in immunocompromised children is similar to that in adults.[58, 59] Infection is a frequent source of morbidity but is rarely fatal. The severity of disease is proportional to the deficiency of cellular immune responses.

It is characterized by the presence of oral and genital lesions that progress slowly to involve contiguous mucosal surfaces and cause esophageal, tracheal or pulmonary involvement, leading to disseminated infection.

Other herpes simplex virus infections

Herpes simplex virus infection of the tip of the finger is referred to as herpetic whitlow.[60] It presents much as other infections of the fingertip. Associated fever and enlarged regional adenopathy are common. An example is shown in the image below.

Herpes whitlow in an infant. Herpes whitlow in an infant.

Herpes gladiatorum is a manifestation of herpes disease seen in wrestlers.[61] It results in painful herpes simplex virus lesions, frequently with numerous cutaneous vesicles. An example is shown in the image below.

Herpes gladiatorum in an adolescent wrestler. Herpes gladiatorum in an adolescent wrestler.

Keratoconjunctivitis manifests with acute onset of pain, watery discharge, itching, blurred vision, lid swelling, and conjunctival injection.[62] Acute retinal necrosis can result in blindness.

Mollaret meningitis, (a recurrent aseptic meningitis) is rarely associated with herpes simplex virus.[63] Low-grade fever, headache, and myalgias may occur with these episodes. Approximately 50% of patients have transitory neurologic symptoms of meningeal irritation. The disease usually spontaneously remits over days.

Herpes simplex virus is one of the most common precipitating factors for erythema multiforme (EM).[64] Approximately 15% of patients with EM provide a history of recurrent herpes simplex virus infections before the characteristic skin lesions erupt.

Eczema herpeticum refers to herpes simplex virus infection superimposed on atopic dermatitis. The incidence of eczema herpeticum in children with atopic dermatitis is between 3-6%.[65]  Risk factors for hospitalization of children with eczema herpeticum include young age (3-4 years) and non-white, non-Hispanic races/ethnicities.[66]   

Physical

Neonatal infections

Skin lesions in SEM disease appear as macules which progress rapidly to vesicles on an erythematous base in areas of trauma, most commonly the site of insertion of a fetal scalp electrode (but also the oropharynx, circumcision site, or the presenting part).[19] Vesicular scalp lesions are shown in the image below.

Vesicular scalp lesions caused by herpes simplex v Vesicular scalp lesions caused by herpes simplex virus (HSV) in a 7-day-old infant.

Herpes simplex virus CNS disease usually presents between the ages of 2-3 weeks with lethargy and focal seizures.[6] Skin lesions are present in about 50% of patients. Cerebrospinal fluid (CSF) examination reveals pleocytosis and modestly elevated protein. The electroencephalogram is diffusely abnormal.

Disseminated herpes simplex virus disease in neonates usually mimics severe bacterial infection, and can present within the first few days of life. Skin lesions are often absent at the onset of illness but 70% of the patients demonstrate skin lesions at some point during the illness. Disease manifestations may include vascular instability, jaundice, hepatomegaly, and pneumonitis.[58]

 

Orolabial herpes simplex virus infections[67]

Primary herpetic gingivostomatitis results in vesicles and ulcers involving the hard and soft palate, gingiva, tongue, and lips. These lesions are initially vesicular, but rupture fairly rapidly, leaving 1-3 mm, shallow, gray-white ulcers on erythematous bases. Fever and cervical and/or submandibular adenopathy are common.

Patients with herpes simplex virus pharyngotonsillitis typically present with ulcers and exudates on the posterior pharynx and tonsillar area. Lesions may also be noted on the tongue, buccal mucosa, or gingiva. Fever may last 2-7 days. Cervical adenopathy is common.

Recurrent orolabial herpetic infection is preceded by a prodrome of pain, burning, tingling, and itching. The prodrome is followed by the emergence of painful vesicles 24-48 hours later. The vesicles evolve into pustules and heal by crusting. Lesions most frequently appear on the vermillion border of the lip.

Genital infections

The rash of primary genital herpes initially appears as macular and papular lesions, followed by a distribution of vesicles, blisters and pustules, with eventual rupture and formation of ulcers. Fever and localized inguinal adenopathy are frequently noted. Lesions are typically observed on labia majora, labia minora, and mons pubis in females and on the shaft of the penis in males.[68, 26]

The painful and tender lesions are associated with dysuria and may involve the buttocks, perineum, and vagina. Urinary retention is observed in 10-15% of female patients.

As many as 25% of women with genital herpes simplex virus have findings suggestive of meningitis.

Symptomatic recurrent herpes simplex virus infection can cause ulcerating vesicular lesions to appear (which are typically few in number and localized), or may manifest as merely irritation of the vulva in women.[18]

Herpes simplex virusCNS disease

Disease occurs in those aged 5-30 years and older than 50 years.

Patients typically have malaise, irritability, and nonspecific symptoms lasting 1-7 days followed by acute onset of fever and focal neurologic signs.[54]

CSF analysis reveals pleocytosis with lymphocytic predominance. In the past, increased RBCs in the CSF were considered suggestive of CNS infection; however, with earlier recognition and diagnosis that laboratory finding is rare today.[11]

Electroencephalography may demonstrate paroxysmal lateralizing epileptiform discharges (PLEDs) but more commonly shows focal spike and slow-wave abnormalities.

Edema with hemorrhagic necrosis is observed on MRI of the brain.

Herpes simplex virusin the immunocompromised patient

Patients with primary immunodeficiencies, AIDS, malignancy, malnutrition, burns, and transplant recipients (eg, bone marrow, organs) receiving immunosuppressive therapy can have unusually severe herpes simplex virus infections.

Severe orolabial infections may begin as typical herpes simplex virus lesions in or around the mouth. Over several days, the papules and vesicles can progress to bullae, frequently with hemorrhagic fluid. These bullae then may evolve into large, chronic, bloody lesions that coalesce and erode into the subcutaneous tissue or deeper tissues.

Orolabial herpes simplex virus infection may involve contiguous mucosal surfaces to cause herpes simplex virus esophagitis, tracheitis, pneumonitis, or disseminated infection. Patients with esophagitis typically present with fever, retrosternal pain, and odynophagia, and patients with pneumonitis present in respiratory failure.

Otherherpes simplex virusinfections

Herpes simplex virus infection of the eye presents as blepharitis, follicular conjunctivitis, or keratoconjunctivitis. Signs include corneal or conjunctival injection, watery discharge, lid swelling, and preauricular adenopathy.

Patients with Mollaret meningitis present with fever, nuchal rigidity, and transitory neurologic findings that accompany meningeal irritation.

Patients with eczema herpeticum are more frequently affected over the head, neck, and trunk than elsewhere on the body. Although the lesions begin to appear over eczematous areas of skin, they can spread to involve normal areas of skin approximately 7-10 days into the course of the illness. Lesional spread to the eye can cause keratoconjunctivitis. Fevers are present in approximately half of children with eczema herpeticum.[65] Secondary bacterial infections with staphylococci and streptococci are present in up to 90% of children with eczema herpeticum.[69]  

 

DDx

 

Workup

Laboratory Studies

Polymerase chain reaction (PCR) is the preferred diagnostic method for herpes simplex virus infections, particularly CNS infection[8, 9, 10] and disseminated disease.

A definitive diagnosis of herpes simplex virus (HSV) infection can also be confirmed by isolating the virus in tissue cultures.

Obtain scrapings of skin vesicles and mucosal lesions and expeditiously transfer them in appropriate viral-transport media to a diagnostic virology laboratory. A cytopathic effect usually develops within 24-48 hours after inoculation of any specimens containing infectious virus. Culture sensitivity may be improved with low-speed centrifugation or ultracentrifugation of the sample directly onto monolayers in centrifuge tubes (shell vials). Immunofluorescent staining of infected tissue culture cells helps in quickly identifying herpes simplex virus as being type 1 or 2.

A skin scraping of the lesion may reveal histologic appearances characteristic of herpesvirus infection, such as multinucleated giant cells and epithelial cells containing intranuclear inclusion bodies. Punch biopsy can provide optimal tissue for histologic diagnosis of a herpesvirus infection, particularly with atypical-appearing lesions.

A Tzanck preparation (see Procedures) may demonstrate the characteristic cytologic changes noted with herpesvirus infection. Cytologic examination via Tzanck testing has low sensitivity (approximately 60-70%), however; as such, use of that testing for diagnosis of herpes simplex virus infection is discouraged.[11, 18, 70]

Serologic diagnosis is of little clinical use. Therapeutic decisions cannot be delayed until serologic results become available.

Serologic testing is of value only to determine past exposure to herpes simplex virus. It may be helpful in demonstrating a primary seroconversion. Because of antibody cross-reactivity, herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) antibodies are not generally distinguishable unless a glycoprotein G antibody assay is used. Transplacental transfer of maternal herpes simplex virus antibody renders interpretation in neonates difficult.

Evaluation of cerebrospinal fluid (CSF) specimens from patients with biopsy-proven herpes simplex virus encephalitis and in those with other proven diseases has a sensitivity of greater than 95% and a specificity that approaches 100% at the time of clinical presentation. Overall sensitivities of PCR in neonatal herpes simplex virus disease range from 75-100%, with overall specificities of 71-100%.[10]

PCR results are positive early in the course of herpes simplex virus encephalitis and remain positive during the first week of therapy. PCR may be used to detect herpes simplex virus in skin lesions.

Herpes simplex virus PCR results should be interpreted cautiously because neither the specificity nor the sensitivity of the analyses is 100%. In addition, performance of these tests may vary among laboratories. Failure to detect HSV DNA by PCR testing of genital lesion swabs does not necessarily rule out a diagnosis of HSV infection, as viral shedding can be intermittent.[11] Testing results should be correlated with clinical manifestations and the course of illness in determining their diagnostic significance.

One study evaluated the utility of quantitative herpes simplex virus PCR levels for prognosis and management of neonatal HSV disease and found a correlation between plasma HSV levels and clinical presentation of neonatal HSV disease and mortality, but not neurologic outcome.[71]

Following analysis of data extracted from the Pediatric Health Information System (PHIS) database, Gaensbauer et al reported that strategies for diagnosis and empirical treatment of suspected HSV encephalitis beyond the neonatal period have trended toward the approach common for neonates without evidence of an increase in disease incidence.[72]

Additional laboratory evaluations (e.g., evaluation of CSF) are necessary in evaluating disseminated infection or infection involving single or multiple organ systems.

A slide prepared from scrapings of lesions may be examined for herpes simplex virus antigens by using immunofluorescent microscopy. Herpes simplex virus type-specific monoclonal antibodies, which are available in commercial antibody staining kits, permit the identification and typing of isolates in tissue samples. Slides containing cells from suspected herpes simplex virus lesions or specimens should be fixed with ethanol or methanol and immediately transported to the laboratory for analysis.

In patients with Mollaret meningitis, analysis of CSF reveals a mixed pleocytosis with neutrophils, lymphocytes, and endothelial cells (Mollaret cells).

Imaging Studies

In patients with herpes simplex virus encephalitis, CT scans and MRI typically reveal focal abnormalities, frequently in the temporal lobe, that may be associated with edema and hemorrhagic necrosis (see the image below).

MRI shows abnormal signal intensity in the left te MRI shows abnormal signal intensity in the left temporal lobe of an 18-year-old man with herpes simplex virus (HSV) encephalitis.

Imaging can also be useful in providing information that suggests etiologies other than herpes simplex virus.

Other Tests

The electroencephalogram is diffusely abnormal in neonates with CNS herpes simplex virus.

Electroencephalography may demonstrate paroxysmal lateralizing epileptiform discharges (PLEDs) but more commonly shows focal spike and slow-wave abnormalities.

Procedures

The Tzanck preparation can be used for the cytologic identification of vesicular exanthems caused by herpesviruses. In the event of a positive test, the microscopist cannot differentiate between infections caused by HSV-1, HSV-2, and varicella zoster virus, however.An intact vesicle is aspirated with a sterile tuberculin syringe. This fluid may be submitted for viral isolation. After the vesicle is aseptically unroofed, the base of the lesion is vigorously scraped with a scalpel or a wooden applicator. The resultant material is placed on a slide, air dried, fixed, and stained, usually with Giemsa or Wright stain.

A positive result is denoted by identification of typical multinucleated giant cells or, uncommonly, Cowdry type A intranuclear inclusion bodies. If the examiner is experienced, 40-80% of culture-positive specimens are recognized as positive by cytologic examination. Appropriate immunofluorescent antibody reagents facilitate the identification of different herpesviruses and some viruses other than herpesviruses.

Lumbar puncture (LP) with submission of CSF for the Gram staining, bacterial culture, and other analyses (eg, determination of cell counts, protein, and glucose levels) is essential when patients with encephalitis are evaluated. Hemorrhagic CSF may be found in herpes simplex virus encephalitis. LP is contraindicated in patients with marked increased intracranial pressure.

All patients with neonatal CNS herpes simplex virus infection should undergo repeat LP at the end of intravenous (IV) acyclovir therapy to determine that the CSF specimen is negative for herpes simplex virus on PCR testing by a reliable laboratory and to document end-of-therapy CSF indices.[10]

Historically, brain biopsy results were frequently used to diagnose herpes simplex virus CNS disease and to exclude other potential pathologic processes. PCR is currently the standard diagnostic modality for herpes simplex virus CNS disease. However, if multiple PCR results are negative in a patient who has signs and symptoms strongly suspicious for herpes simplex virus encephalitis, brain biopsy may be contemplated. It is important to note that CSF PCR testing results in patients with HSV encephalitis can be falsely negative when obtained prior to the third day of illness.[18]  

Histologic Findings

Herpes simplex virus infects cells of ectodermal origin.

Infected cells swell with intracellular edema and degeneration.

The nuclei of infected cells undergo mitotic division, resulting in the formation of multinucleated giant cells. The nuclei of herpes simplex virus–infected cells often demonstrate eosinophilic intranuclear inclusions and marginated nuclear chromatin.

As cells manifest injury and as local inflammation progresses, intercellular edema develops and forms vesicles. Cutaneous vesicles eventually progress to pustules and heal by crusting. Mucosal vesicles are transient and appear as shallow ulcers.

 

Treatment

Medical Care

Specific medical therapy of herpes simplex virus (HSV) infections involves antiviral medications. Aggressive inpatient and/or intensive medical care is needed in the management of neonatal herpes simplex virus infections, herpes simplex virus encephalitis, and infections in immunocompromised hosts.

In Mollaret meningitis, therapy is primarily symptomatic because symptoms and signs resolve over days.

Therapy of erythema multiforme (EM) generally addresses the dermatologic manifestations and not just the viral infection.

Consultations

Consultation with physicians experienced in caring for seriously ill patients with infectious diseases is recommended for neonatal herpes simplex virus infections, herpes simplex virus encephalitis or disseminated disease, and herpes simplex virus infection in patients who are immunocompromised. Such physicians may include neonatologists, critical care specialists, and infectious diseases physicians.

A consultation with an ophthalmologist is imperative in the management of herpes simplex virus eye infections.

For a child with genital herpes simplex virus infection that is suspected to be a result of child abuse (see the image below), consultation with social services and/or a physician experienced in managing child and/or sexual abuse is warranted.

Cutaneous herpes simplex virus (HSV) lesions in a Cutaneous herpes simplex virus (HSV) lesions in a child in whom sexual abuse is suspected.
 

Guidelines

Guidelines Summary

AAP clinical practice guidelines

In January 2013, the American Academy of Pediatrics issued new guidelines for the evaluation of asymptomatic neonates exposed to HSV during delivery.[73, 16, 74] The guidelines assume laboratory access to polymerase chain reaction (PCR) assays for HSV DNA or type-specific serologic tests and may not be applicable in clinical settings without rapid testing turnaround times. Recommendations include the following:

  • Women in labor with visible genital lesions should be swabbed for HSV PCR and culture, and positive test results should be further analyzed to distinguish HSV-1 from HSV-2

  • A history of genital herpes should be obtained before the pregnancy

  • In women with a recurrent maternal herpes outbreak, skin and mucosal specimens should be obtained from the neonate for culture and PCR assay (the latter only if desired) about 24 hours after delivery, and blood should be sent for HSV DNA PCR assay; preemptive treatment with acyclovir need not be started if the infant remains asymptomatic. If results become positive within 5 days, confirming neonatal HSV infection, the infant should undergo a complete evaluation to determine the extent of disease, and intravenous acyclovir should be initiated as soon as possible.

  • In women without a history of genital herpes who have genital lesions at delivery, serologic testing (for HSV-1 IgG and HSV-2 IgG) should be performed on maternal blood samples obtained during delivery to determine the type of infection present (that is, primary versus nonprimary versus recurrent). The infant should undergo a complete evaluation – including obtaining of surface viral cultures of the conjunctivae, naso-/oropharynx, and rectum (and PCRs of those sites if desired), HSV blood PCR, lumbar puncture with obtaining of CSF cell counts and chemistries, HSV CSF PCR, serum ALT, and IV acyclovir should be initiated. If the mother has a first-episode (primary or non-primary) infection and the neonate’s results are normal, the infant should be treated with IV acyclovir for 10 days; if the neonate’s results are positive, the infant should be treated with IV acyclovir for 14-21 days (depending on the extent of disease) and reevaluated to ensure clearance of the virus. After completion of IV acyclovir treatment durations of greater than or equal to 14-21 days, infants should receive suppressive therapy with oral acyclovir for 6 months

 

Medication

Medication Summary

Antiviral agents used to treat herpes simplex virus infections are nucleoside analogs. Acyclovir is the antiviral most commonly used to treat herpes simplex virus (HSV) infections. Other oral medications include famciclovir, which is a prodrug that is converted to penciclovir, and valacyclovir, which is a prodrug that is converted to acyclovir. Oral therapy is effective for non–life-threatening herpes simplex virus infections (eg, primary orolabial, genital), and can be useful in the suppression of recurrent genital herpes simplex virus infections to diminish viral shedding and decrease rates of clinical recurrences. Intravenous (IV) acyclovir is indicated for the treatment of encephalitis, any form of neonatal disease, severe infection in patients who are immunocompromised, and occasionally for cases of severe orolabial or genital disease.[11, 12, 13, 14]

Antiviral agents

Class Summary

Acyclovir, a synthetic acyclic purine nucleoside analog, is the standard treatment for herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infections. Activation of the drug requires 3 phosphorylations. Herpes simplex virus thymidine kinase adds the first phosphate. Acyclovir binds 200-300 times more avidly to viral thymidine kinase than to host enzyme. After final cellular phosphorylation, the nucleoside triphosphate effectively inhibits DNA polymerase and acts as a DNA chain terminator. Precursors of acyclovir (ie, valacyclovir, famciclovir) have bioavailability better than that of their active metabolites (acyclovir and penciclovir, respectively). The bioavailability of valacyclovir ranges from approximately 42-64%, while that of acyclovir is between 10-20%.[75]  

The results of a multicenter, retrospective, cohort study suggest that delayed initiation of acyclovir therapy was associated with significantly greater odds of death in neonates with HSV infection.[76]

Acyclovir (Zovirax)

Inhibits activity of HSV-1 and HSV-2. Patients experience least pain and fastest resolution of cutaneous lesions with prompt start of therapy, usually within 48 h after rash onset. Selectively incorporated into infected cells. May prevent recurrent outbreaks. Long record of use with excellent safety profile.

Available as PO susp 200 mg/5 mL, tab, cap, injection, and topical formulation. Topical form does not appear to be effective in recurrent mucocutaneous or genital HSV infections and offers no advantage over PO form in treating primary genital HSV infections. For obese patients, calculate IV dose according to ideal body weight.

Valacyclovir (Valtrex)

Prodrug rapidly converted to active drug acyclovir. More expensive but more convenient dosing regimen and superior bioavailability than that of PO acyclovir. Use in adolescent HSV infection. Available as 500 mg and 1g tablet formulations. 

Famciclovir (Famvir)

Transformed in vivo to active nucleoside analogue penciclovir, which can effectively inhibit HSV DNA synthesis and/or replication. More expensive but more convenient dosing regimen than that of acyclovir. Use in adolescent HSV infection.

Penciclovir (Denavir)

1% cream approved for treatment of recurrent orolabial HSV infection. Nucleotide derivative active in vitro against HSV-1 and HSV-2. Guanosine analog that inhibits viral DNA synthesis. Negligible systemic absorption after topical use. Repeated application of cream beginning shortly after onset of recurrent HSV symptoms and continued for 4 d shortens healing time to about 1 d. May also shorten duration of viral shedding. Not approved by the FDA for use in children.

 

Follow-up

Further Outpatient Care

Adolescents with genital herpes simplex virus infection may require ongoing care for recurrences of herpes simplex virus infections (see Medication).

With effective antiviral therapy, an increasing number of newborns with herpes simplex virus infection survive and require long-term follow-up care. These children should receive ongoing evaluations from specialists in areas including neurodevelopment, ophthalmology, and audiology.

Parents of a child with neonatal herpes simplex virus infection often have considerable feelings of guilt. Parents often require interventional care. In this situation, support from the primary care physician can be of great value to the family.

Further Inpatient Care

In-patient management is often indicated for patients with herpes simplex virus (HSV) infections.

Some suggested criteria are as follows:

  • Many children with severe herpes simplex virus gingivostomatitis with dehydration for intravenous (IV) fluids and pain management.

  • Neonates with disseminated/CNS disease.

  • Older patients with encephalitis who may be very ill at presentation and need inpatient evaluation and intensive care.

  • Herpes simplex virus infection in immunocompromised patients.

Inpatient & Outpatient Medications

Recurrent herpes simplex virus disease in adolescents may be an indication for long-term suppressive treatment with antiviral medications (see Medication).

Transfer

Transfer should be arranged if the required care is not available locally.

Deterrence/Prevention

Genital herpes simplex virus infections are among the most common sexually transmitted infections (STIs) in the United States. A growing number of adolescents are infected with the virus. Prevention of sexual transmission of herpes simplex virus is difficult because most transmission occurs during subclinical viral shedding. Avoiding contact with individuals excreting the virus in saliva or genital secretions is difficult because they are often asymptomatic.

Oral antiviral therapy started at the first symptom or sign of genital herpes simplex virus disease reduces (but may not eliminate) the duration of lesions, symptoms, and viral shedding in persons with recurrent genital herpes.[68, 77, 78]

Daily suppressive treatment with oral antiviral agents reduces the frequency of recurrences and viral shedding in persons with genital herpes simplex virus infection.[49, 77] It may also improve psychosocial functioning.

In 2016, the US Preventive Services Task Force (USPSTF) recommended against routine serologic screening for genital herpes simplex virus infection in asymptomatic adolescents and adults, including those who are pregnant.[79, 80]

Promote the use of condoms.

Patients with history of genital herpes simplex virus infection may have been exposed to or are at risk of continued exposure to other STIs. Appropriate evaluation, counseling, and education are needed for all patients.

The transmission of herpes simplex virus from mother to infant cannot be eliminated because of asymptomatic primary or recurrent genital infection. The high prevalence of herpes simplex virus type 2 (HSV-2) infections in the United States means that women are at risk of acquiring new infections during pregnancy. One in 5 women is infected before pregnancy. Management to prevent transmission of the virus to newborns includes the following:

  • Reassure women with recurrent disease that risk of neonatal infection is low. The risk of asymptomatic reactivation is approximately 2%, and the attack rate in exposed infants is approximately 3%.

  • Because laboratory methods cannot be used to detect asymptomatic shedding in a timely manner, perform cesarean delivery if a mother has active lesions during delivery.[15] Because of the low risk of transmission, a vaginal delivery is appropriate in women with history of recurrent herpes simplex virus disease who have no active clinical disease at delivery.[81]

  • No information is available to support the empiric administration of IV acyclovir to potentially exposed infants who are without signs of infection. Observe infants delivered vaginally by mothers with active genital herpes. At approximately 24 hours, obtain testing as per American Academy of Pediatrics guidelines (see Guidelines Summary). In women with symptomatic genital herpes, antiviral suppressive treatment initiated at 36 weeks' gestation reduced both the rates of cesarean delivery due to HSV lesions and positive viral cultures or polymerase chain reaction (PCR) tests at the time of delivery.[31, 40, 82, 83] However, data are insufficient to recommend antiviral suppressive therapy to pregnant women who are HSV-2 seropositive and asymptomatic.[84, 81] Furthermore, such antenatal antiviral suppressive therapy does not completely prevent herpes disease in the newborns of mothers who receive it.[85]

Complications

Complications of cutaneous herpes simplex virus infections in children and adolescents include eczema herpeticum in children with underlying atopic skin disease, herpetic whitlow of the fingers, and herpes gladiatorum in wrestlers (see History, Physical). Secondary bacterial infections can also occur.

Herpes simplex virus infection of the visceral organs results from viremia with dissemination to many organs. Although this disease is most common in the immunocompromised population, it can also occur in immunologically healthy individuals. Most cases reflect disseminated skin disease, though multiple organs may be involved and hepatitis may be prominent. Disseminated infection can also result in esophagitis, pneumonitis, encephalitis, and adrenal necrosis. Leukopenia, thrombocytopenia, and disseminated intravascular coagulation are not uncommon.

Newborns with herpes simplex virus skin disease may have recurrences for months to years, particularly with HSV-2 disease, even if antiviral therapy was appropriately administered. The role of suppressive oral antiviral therapy with acyclovir in prevention of these cutaneous herpes simplex virus recurrences is an area of active investigation.[86]

Prognosis

Herpes simplex virus infections beyond the fetal and neonatal period are usually associated with increased morbidity but are not life threatening.

Herpes simplex virus encephalitis is a serious disease that can result in clinically significant neurologic impairment or death. The mortality rate is approximately 70% in untreated patients and 19% in treated patients.[19] Even after treatment, survivors have some neurologic impairment (impaired learning, dysnomia) noted upon detailed clinical cognitive testing.

Even with antiviral therapy, neonatal herpes simplex virus infection is associated with significant morbidity and mortality. Death typically does not occur after skin, eye, and mucus membrane (SEM) disease is treated, but 12-month mortality rates approach 4% with neonatal CNS disease and 29% with disseminated disease. Among neonates treated with antivirals, 2% of children with SEM disease, 69% of children with herpes simplex virus–related CNS disease, and 17% of children with disseminated herpes simplex virus disease develop evidence of neurologic impairment 2 years after infection.[19, 87]

The results of one study noted that infants who survived neonatal herpes simplex virus infection with CNS involvement who received suppressive therapy with oral acyclovir (300 mg/m2/dose PO tid for 6 mo) had significantly higher mean Bayley mental-development scores at 12 months than did infants who did not.[87] Another multicenter, retrospective, cohort study suggest that delayed initiation of acyclovir therapy was associated with significantly greater odds of death in neonates with herpes simplex virus infection.[76]

Genital herpes simplex virus infection may not be life threatening but is an important cause of physical and psychological morbidity.

Patient Education

Because increasing rates of STIs are occurring in adolescents, offer patients regular and appropriate education in sexual health as well as in the diagnosis and treatment of their diseases. The presence of an STI should prompt assessment and potential treatment for other infections (eg, chlamydia, HIV infection, syphilis, hepatitis B, hepatitis C).

Antiviral therapy may decrease the duration of clinical manifestations of herpes simplex virus disease but does not cure the infection.

Initiate antiviral therapy as soon as possible after signs and symptoms of disease are noted.

Daily suppressive management with oral antiviral agents reduces the frequency of herpes simplex virus recurrences and viral shedding. Consider antiviral suppressive therapy in adolescents with frequent genital recurrences (6 or more per year).

Condom use decreases the risk of the sexual transmission of HSV-2[88] .

For patient education resources, see the Sexually Transmitted Diseases Center, as well as Genital Herpes, Birth Control Overview, and Birth Control FAQs.

 

Questions & Answers

Overview

How are herpes simplex virus (HSV) infections transmitted?

What are the clinical presentations of herpes simplex virus (HSV)?

What are the signs and symptoms of orolabial herpes simplex virus (HSV) infection?

What are the signs and symptoms of genital herpes simplex virus (HSV) infection?

How is herpes neonatorum categorized?

What are the signs and symptoms of herpes simplex virus (HSV) infection of the CNS?

How is herpes simplex virus (HSV) infection diagnosed in children?

Which antiviral agents are used for the treatment of herpes simplex virus (HSV) in neonates?

What are the indications for inpatient management of pediatric herpes simplex virus (HSV) infections?

How is transmission of genital herpes simplex virus (HSV) infection prevented?

How is transmission of herpes simplex virus (HSV) to newborns prevented?

What is herpes simplex virus (HSV)?

What is the pathophysiology of herpes simplex virus (HSV) infection?

What is the prevalence of herpes simplex virus (HSV) in the US?

What is the global prevalence of herpes simplex virus (HSV)?

What causes mortality in herpes simplex virus (HSV) infections?

What is the risk of herpes simplex virus (HSV) transmission from a mother to her infant?

What is the incidence of neonatal herpes simplex virus (HSV) infection?

What are the racial predilections of herpes simplex virus (HSV) infection?

How does the incidence of herpes simplex virus (HSV) vary by sex?

How does the prevalence of herpes simplex virus (HSV) infection vary by age?

Presentation

What is the clinical presentation of herpes simplex virus (HSV) infection?

What is the common clinical presentation of primary orolabial herpes simplex virus (HSV) infection?

What are the signs and symptoms of primary orolabial herpes simplex virus (HSV) infection?

What are the signs and symptoms of reactivation of orolabial herpes simplex virus (HSV) infection?

What is the presentation of primary genital herpes simplex virus (HSV) infections?

What is are the signs and symptoms of reactivation of genital herpes simplex virus (HSV) infections?

Why is the rate of intrauterine and perinatal herpes simplex virus (HSV) infection highest in neonates exposed to primary maternal infections?

How is herpes neonatorum categorized?

What are the signs and symptoms of herpes simplex virus (HSV) infection of the CNS?

What is the presentation of herpes simplex virus (HSV) infection in immunocompromised patients?

What are less common manifestations of herpes simplex virus (HSV) infections?

Which physical findings are characteristic of neonatal herpes simplex virus (HSV) infections?

Which physical findings are characteristic of orolabial herpes simplex virus (HSV) infections?

Which physical findings are characteristic of genital herpes simplex virus (HSV) infections?

Which physical findings are characteristic of herpes simplex virus (HSV) infections of the CNS?

Which physical findings are characteristic of herpes simplex virus (HSV) infection in the immunocompromised patient?

Which physical findings are characteristic of ocular herpes simplex virus (HSV) infections?

DDX

What are the differential diagnoses for Pediatric Herpes Simplex Virus Infection?

Workup

What is the preferred method for diagnosis of herpes simplex virus (HSV) infections?

What is the role of skin scrapings in the workup of herpes simplex virus (HSV)?

What is the role of Tzanck preparation in the workup of herpes simplex virus (HSV) infections?

What is the role of serologic diagnosis in the management of herpes simplex virus (HSV)?

What is the role of cerebrospinal fluid (CSF) analysis in the evaluation of herpes simplex virus (HSV)?

What is the role of PCR in the workup of herpes simplex virus (HSV) infections?

What is the role of immunofluorescent microscopy in the workup of herpes simplex virus (HSV) infection?

Which CSF findings suggest Mollaret meningitis in herpes simplex virus (HSV) infection?

What is the role of imaging studies in the workup of herpes simplex virus (HSV) infections?

What is the role of electroencephalography in the workup of herpes simplex virus (HSV) infection?

Which procedures may be helpful in the diagnosis of herpes simplex virus (HSV) infection?

Which histologic findings are characteristic of herpes simplex virus (HSV) infection?

Treatment

What are medical care options for herpes simplex virus (HSV) infection?

Which specialist consultations may be needed for the treatment of herpes simplex virus (HSV)?

Guidelines

What are the American Academy of Pediatrics (AAP) guidelines for the evaluation of asymptomatic neonates exposed to herpes simplex virus (HSV) during delivery?

Medications

Which antiviral agents are used in the treatment of herpes simplex virus (HSV) infections?

Which medications in the drug class Antiviral agents are used in the treatment of Pediatric Herpes Simplex Virus Infection?

Follow-up

What is included in long-term monitoring of pediatric herpes simplex virus (HSV) infection?

When is inpatient management indicated for herpes simplex virus (HSV) infections?

How is recurrent herpes simplex virus (HSV) infection treated?

What is the indication for transfer in herpes simplex virus (HSV) infections?

How is genital herpes simplex virus (HSV) infection prevented?

How is transmission of herpes simplex virus (HSV) from mother to infant prevented?

What are complications of herpes simplex virus (HSV) infection?

What is the prognosis of herpes simplex virus (HSV) infections?

What should be included in patient education for herpes simplex virus (HSV) infections?