eMedicine Specialties > Infectious Diseases > Viral Infections

Herpes Simplex

Author: Michelle R Salvaggio, MD, Assistant Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine; Medical Director of Infectious Diseases Institute, University of Oklahoma Health Sciences Center
Coauthor(s): Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus; Meena Seenivasan, MD, Fellow, Department of Infectious Disease, State University of New York Health Science Center at Brooklyn; Swati Kumar, MD, Assistant Professor of Pediatrics, Division of Infectious Diseases, Medical College of Wisconsin, Consulting Staff, Children's Specialty Group, Children's Hospital of Wisconsin
Contributor Information and Disclosures

Updated: May 27, 2009

Introduction

Background

Herpes simplex viruses are ubiquitous, host-adapted pathogens that cause a wide variety of disease states. Two types exist: herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Both are closely related but differ in epidemiology. HSV-1 is traditionally associated with orofacial disease, while HSV-2 is traditionally associated with genital disease; however, lesion location is not necessarily indicative of viral type.

Up to 80% of herpes simplex infections are asymptomatic. Symptomatic infections can be characterized by significant morbidity and recurrence. In immunocompromised hosts, infections can cause life-threatening complications.

The prevalence of HSV infection worldwide has increased over the last several decades, making it a major public health concern. Prompt recognition of herpes simplex infection and early initiation of therapy are of utmost importance in the management of the disease.

Pathophysiology

HSV (both types 1 and 2) belongs to the family Herpesviridae and to the subfamily Alphaherpesvirinae. It is a double-stranded DNA virus characterized by the following unique biological properties:¹

• Neurovirulence (the capacity to invade and replicate in the nervous system)
• Latency (the establishment and maintenance of latent infection in nerve cell ganglia proximal to the site of infection): In orofacial HSV infections, the trigeminal ganglia are most commonly involved, while, in genital HSV infection, the sacral nerve root ganglia (S2-S5) are involved.
• Reactivation: The reactivation and replication of latent HSV, always in the area supplied by the ganglia in which latency was established, can be induced by various stimuli (eg, fever, trauma, emotional stress, sunlight, menstruation), resulting in overt or covert recurrent infection and shedding of HSV. In immunocompetent persons who are at an equal risk of acquiring HSV-1 and HSV-2 both orally and genitally, HSV-1 reactivates more frequently in the oral rather than the genital region. Similarly, HSV-2 reactivates 8-10 times more commonly in the genital region than in the orolabial regions. Reactivation is more common and severe in immunocompromised individuals.²

Dissemination of herpes simplex infection can occur in people with impaired T-cell immunity, such as in organ transplant recipients and in individuals with AIDS.

HSV is distributed worldwide. Humans are the only natural reservoirs, and no vectors are involved in transmission. Endemicity is easily maintained in most human communities owing to latent infection, periodic reactivation, and asymptomatic virus shedding.³

HSV is transmitted by close personal contact, and infection occurs via inoculation of virus into susceptible mucosal surfaces (eg, oropharynx, cervix, conjunctiva) or through small cracks in the skin. The virus is readily inactivated at room temperature and by drying; hence, aerosol and fomitic spread are rare.

Frequency

United States

HSV is ubiquitous, and most individuals show some evidence of HSV infection. HSV-1 is usually acquired in childhood by contact with oral secretions that contain the virus. The presence of HSV-2 can be used as an indirect measure of sexual activity in some cases. Seroprevalence rates do not reflect how many of these individuals have or will have symptomatic episodes of HSV recurrence.

Seroprevalence: Antibodies to HSV-1 increase with age starting in childhood and correlate with socioeconomic status, race, and cultural group. By age 30 years, 50% of individuals in a high socioeconomic status and 80% in a lower socioeconomic status are seropositive. Antibodies to HSV-2 begin to emerge at puberty, correlating with the degree of sexual activity. The lifetime seroprevalence can be 20%-80%.⁴

International

HSV is well distributed worldwide. An increase in seroprevalence of antibodies to HSV-2 has been documented throughout the world (including the United States) over the last 20 years.¹

Mortality/Morbidity

Morbidity and mortality rates associated with HSV infections are discussed in Complications. Overall, the mortality rate associated with herpes simplex infections is related to 3 situations: perinatal infection, encephalitis, and infection in the immunocompromised host.

Race

The most recent national health survey conducted in the United States revealed a seroprevalence of HSV-2 antibodies in 45% of blacks, 22% of Mexican-Americans, and 17% of whites.⁴

Sex

Seropositivity to antibodies to HSV-2 is more common in women (25%) than in men (17%).⁴

Age

HSV-1 infections transmitted via saliva are common in children, although primary herpes gingivostomatitis can be observed at any age. HSV-2 infections are clustered perinatally (from a maternal episode at delivery) and primarily once sexual activity begins. HSV-2 genital infections in children can be an indication of sexual abuse. Increased age (after onset of sexual activity) and total number of sexual partners are independent factors associated with increased seroprevalence of HSV-2 antibodies.⁴

Clinical

History

The clinical course of herpes simplex infection depends on the age and immune status of the host, the anatomic site of involvement, and the antigenic virus type. Primary herpes simplex virus (HSV)–1 and HSV-2 infections are accompanied by systemic signs, longer duration of symptoms, and higher rate of complications. Recurrent episodes are milder and shorter. Both HSV-1 and HSV-2 can cause similar genital and orofacial primary infections after contact with infectious secretions containing either HSV-1 (usually oral secretions) or HSV-2 (usually genital secretions).

• Acute herpetic gingivostomatitis⁵
  • This is a manifestation of primary HSV-1 infection that occurs in children aged 6 months to 5 years. Adults may also develop acute gingivostomatitis, but it is less severe and is associated more often with a posterior pharyngitis.
  • Infected saliva from an adult or another child is the mode of infection. The incubation period is 3-6 days.
  • Clinical features include the following:
    • Abrupt onset
    • High temperature (102-104°F)
    • Anorexia and listlessness
    • Gingivitis (This is the most striking feature, with markedly swollen, erythematous, friable gums.)
    • Vesicular lesions (These develop on the oral mucosa, tongue, and lips and later rupture and coalesce, leaving ulcerated plaques.)
    • Tender regional lymphadenopathy
    • Perioral skin involvement due to contamination with infected saliva
  • Course: Acute herpetic gingivostomatitis lasts 5-7 days, and the symptoms subside in 2 weeks. Viral shedding from the saliva may continue for 3 weeks or more.
• Acute herpetic pharyngotonsillitis
  • In adults, oropharyngeal HSV-1 infection causes pharyngitis and tonsillitis more often than gingivostomatitis.
  • Fever, malaise, headache, and sore throat are presenting features.
  • The vesicles rupture to form ulcerative lesions with grayish exudates on the tonsils and the posterior pharynx.
  • Associated oral and labial lesions occur in fewer than 10% of patients.
  • HSV-2 infection can cause similar symptoms and can be associated with orogenital contact or can occur concurrently with genital herpes.
• Herpes labialis⁶
  • This is the most common manifestation of recurrent HSV-1 infection. A prodrome of pain, burning, and tingling often occurs at the site, followed by the development of erythematous papules that rapidly develop into tiny, thin-walled, intraepidermal vesicles that become pustular and ulcerate. In most patients, fewer than two recurrences manifest each year, but some individuals experience monthly recurrences.
  • Maximum viral shedding is in the first 24 hours of the acute illness but may last 5 days.
• Genital herpes: The severity and frequency of the disease and the recurrence rate depend on numerous factors, including viral type, prior immunity to autologous or heterologous virus, gender, and immune status of the host.^7,2
• Primary genital herpes
  • Primary genital herpes can be caused by both HSV-1 and HSV-2 and can be asymptomatic. The clinical features and course of primary genital herpes caused by both HSV-1 and HSV-2 are indistinguishable, but recurrences are more common with HSV-2.
  • Primary genital herpes is characterized by severe and prolonged systemic and local symptoms. The symptoms of persons with a first episode of secondary HSV-2 infection are less severe and of shorter duration.
  • Preexisting antibodies to HSV-1 have an ameliorating effect on disease severity caused by HSV-2.
  • Prior orolabial HSV-1 infection protects against genital HSV-1 but not HSV-2.
  • Symptoms of primary genital herpes are more severe in women, as are complications.
  • Clinical features: The incubation of primary genital herpes period is 3-7 days (range, 1 d to 3 wk). Constitutional symptoms include fever, headache, malaise, and myalgia (prominent in the first 3-4 d). Local symptoms include pain, itching, dysuria, vaginal and urethral discharge, and tender lymphadenopathy.
  • Clinical features in women: Herpetic vesicles appear on the external genitalia, labia majora, labia minora, vaginal vestibule, and introitus. In moist areas, the vesicles rupture, leaving exquisitely tender ulcers. The vaginal mucosa is inflamed and edematous. The cervix is involved in 70%-90% of cases and is characterized by ulcerative or necrotic cervical mucosa. Cervicitis is the sole manifestation in some patients. Dysuria may be very severe and may cause urinary retention. Dysuria is associated with urethritis, and HSV can be isolated in the urine. HSV-1 infection causes urethritis more often than does HSV-2 infection.
  • Clinical features in men: Herpetic vesicles appear in the glans penis, the prepuce, the shaft of the penis, and sometimes on the scrotum, thighs, and buttocks. In dry areas, the lesions progress to pustules and then encrust. Herpetic urethritis occurs in 30%-40% of affected men and is characterized by severe dysuria and mucoid discharge. The perianal area and rectum may be involved in persons who engage in anal intercourse, resulting in herpetic proctitis.
  • In men and women, the ulcerative lesions persist from 4-15 days until encrusting and reepithelialization occur. New lesions occur during the course of the illness in 75% of patients, usually forming in 4-10 days. The median duration of viral shedding is about 12 days.
• Recurrent genital herpes
  • The major morbidity of genital herpes is due to its frequent reactivation rate. In one study, 90% of patients reactivated within the first 12 months. In patients with HSV-2 infection, 38% had 6 recurrences in 1 year, and 20% had more than 10 recurrences in the first year.
  • Both subclinical and symptomatic reactivation is more common in HSV-2 infection than in HSV-1 infection. Sixty percent of patients with primary genital HSV-2 infection experience recurrences in the first year.
  • Patients who had severe primary genital herpes tend to have more frequent recurrences of longer duration.
  • Recurrent genital herpes is preceded by a prodrome of tenderness, pain, and burning at the site of eruption that may last from 2 hours to 2 days. In some patients, severe ipsilateral sacral neuralgia occurs.
  • In women, the vesicles are found on the labia majora, labia minora, or perineum. The lesions are often very painful. Fever and constitutional symptoms are uncommon. The lesions heal in 8-10 days, and viral shedding lasts an average 5 days. The symptoms are more severe in women than men.
  • In men, recurrent genital herpes presents as 1 or more patches of grouped vesicles on the shaft of the penis, prepuce, or glans. Urethritis is uncommon. Pain is mild, and lesions heal in 7-10 days. The frequency and severity of recurrences decrease with time.²
• Subclinical genital herpes
  • Most primary genital HSV infections are asymptomatic, with 70%-80% of seropositive individuals having no history of known genital herpes. However, upon education regarding the varied clinical manifestations, many patients recognize the symptoms of genital herpes.
  • Truly asymptomatic viral shedding may occur in 1%-2% of infected immunocompetent persons and may be as high as 6% in the first few months after acquisition of the infection.^3,8 This property is important when attempting to prevent transmission sexually or perinatally.

Physical

This section describes physical examination findings of the herpetic lesion as it relates to primary and recurrent lesions of cutaneous or mucosal HSV infection. This can be related to either oral or genital infection.^1,2,5

• Primary mucocutaneous HSV infections
  • Some primary infections are asymptomatic.
  • Primary (first-episode) infections manifest within several days of exposure to secretions containing viable virus.
  • Often painful, the lesions quickly progress to vesicles and can continue to erupt over 1-2 weeks.
  • The lesions are prominent and are often present internally on the mucosal surface of the oral or genital area, as well as on the surrounding skin.
  • Constitutional symptoms (fever, malaise, myalgias, and anorexia) are often prominent. Weight loss is not uncommon and is due either to illness or dysphagia (in primary gingivostomatitis).
  • Individual vesicles on mucosal surfaces break down rapidly, forming shallow painful ulcers (usually <8-10 mm in diameter). They may be covered with a white exudate that can be confused with mucosal candidiasis. Those on cutaneous surfaces remain as vesicles longer, only to evolve into crusted ulcers that heal within 5-7 days.
• Recurrent mucocutaneous HSV infections
  • Following the establishment of latency in the corresponding sensory nerve ganglion cells, HSV can cause recurrent infection that can be subclinical (manifesting as viral excretion without lesions) or overt (manifesting as mucosal or cutaneous lesions with viral excretion).
  • Oral recurrences are often triggered by recognizable stimuli such as pyrexia (fever blisters and cold sores), stress, or sunburn. Genital recurrences are more likely to be linked to stress rather than to pyrexia. Females may relate a relationship to the menstrual cycle.
  • Localized burning or paraesthesias may precede recurrent lesions. Unlike primary infection, constitutional symptoms are minimal in most cases.
  • Recurrences last 3-7 days and can occur numerous times per year or once or twice in a lifetime. Overall, the number of yearly recurrences tends to decrease over time.⁹
  • Although recurrent HSV infections may last much longer (>30 d) in immunocompromised hosts, such as individuals with AIDS, frequent recurrences are not necessarily a sign of an altered immune system.
  • Because recurrences can be clinically unrecognizable, transmission to susceptible individuals can occur in the absence of overt lesions. In genital HSV infections, barrier protection should be used regardless of existing lesions, even in the absence of a history of genital HSV infection.
  • Vesicles occurring in a sacral dermatomal distribution (zosteriform) can occur in recurrent genital HSV disease and be confused with herpes zoster. A history of similar recurrences should alert the clinician to this possibility.
  • Sacral HSV infection recurrences also may present with signs and symptoms of meningeal inflammation; and, in fact, a picture consistent with aseptic meningitis can be found upon examination of the cerebrospinal fluid (CSF).¹⁰

Causes

• HSV is transmitted via close personal contact.
• HSV infection occurs via inoculation of virus into susceptible mucosal surfaces (eg, oropharynx, cervix, conjunctiva) or through small cracks in the skin.
• The virus is inactivated readily at room temperature and by drying; hence, aerosol and fomitic spread are rare.
• HSV-1 is transmitted chiefly by contact with infected saliva, whereas HSV-2 is transmitted sexually or from a mother's genital tract infection to her newborn. However, lesion location does not always indicate viral type.

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