History
HSV can cause either primary or reactivation (recurrent) infections. Both HSV-1 and HSV-2 are implicated in genital and orofacial primary infections after contact with infectious secretions that contain either HSV-1 (usually oral secretions) or HSV-2 (usually genital secretions). The clinical course depends on the age and immune status of the host, the anatomic site of involvement, and the antigenic virus type. Primary HSV-1 and HSV-2 infections are accompanied by systemic signs, longer duration of symptoms, and higher rate of complications. Recurrent infections are typically milder and shorter. HSV infections in immunocompromised host tend to be more severe, prolonged, and widespread and are more likely to recur than HSV infections in immunocompetent individuals.
Acute herpetic gingivostomatitis
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. [9]
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:
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Abrupt onset
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High temperature (102-104°F)
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Anorexia and listlessness
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Gingivitis (This is the most striking feature, with markedly swollen, erythematous, friable gums.)
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Vesicular lesions (These develop on the oral mucosa, tongue, and lips and later rupture and coalesce, leaving ulcerated plaques.)
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Tender regional lymphadenopathy
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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 labialis
This is the most common manifestation of recurrent HSV-1 infection, referred to by many as ”cold sores.” A prodrome of pain, burning, and tingling often occurs at the affected site, commonly the face, around the lips, 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. [10]
Maximum viral shedding is in the first 24 hours of the acute illness but may last 5 days.
Herpetic whitlow
HSV infection of the finger, termed herpetic whitlow, can occur following inoculation of the virus from primary orofacial or genital infections. Inoculation may occur from self or from other infected persons. Healthcare workers, including dentists, are at risk for herpetic whitlow owing to oral examinations and other oral care provided with ungloved hands.
Herpetic whitlow in a young child who earlier had developed herpes gingivostomatitis. Courtesy of Wikimedia Commons [James Heilman, MD] (https://commons.wikimedia.org/w/index.php?search=Herpetic+whitlow+in+a+young+child&title=Special:MediaSearch&go=Go&type=image).
Herpes gladiatorum
Herpes gladiatorum is HSV infection of the face, arms, neck, and upper trunk, typically seen in wrestlers and participants in some contact sports such as rugby. Infection is promoted by trauma to the skin sustained during matches.
Eczema herpeticum
Eczema herpeticum is an extensive cutaneous vesicular eruption that arises from pre-existing skin disease, usually atopic dermatitis. Children have a higher risk of developing eczema herpeticum, in which HSV type 1 (HSV-1) is the most common pathogen. Bacterial superinfection and bacteremia are usually the complications that cause mortality.
Eczema herpeticum; cluster of blisters and punched out erosions of HSV in a child. Courtesy of Wikimedia Commons [Mohammad2018] (https://commons.wikimedia.org/wiki/File:Eczema_herpitcum.jpg).
Genital herpes
Most genital acquisitions (> 85%) are due to oral-to-genital transmission through oral sex, as opposed to genital-to-genital transmission through sexual intercourse. [11] 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. [2]
Primary genital herpes
Primary genital herpes can be caused by both HSV-1 and HSV-2 and can be asymptomatic. HSV-2 tends to have tropism for genital mucosa and has been traditionally more associated with genital infections. However, HSV-1 is increasingly associated with genital infection and has been reported to cause more genital infections than HSV-2, especially in young people and homosexual males. [12, 13] 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. Preexisting antibodies to HSV-1 have an ameliorating effect on disease severity caused by HSV-2. Prior orolabial HSV-1 infection appears to protect against or may lower genital HSV-1 infection risk. Symptoms of primary genital herpes are more severe in women, as are complications. [7, 14, 15, 16]
Clinical features: The incubation period of primary genital herpes is 3-7 days (range, 1 day to 3 weeks). Constitutional symptoms include fever, headache, malaise, and myalgia (prominent in the first 3-4 days). 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. Ulcers are seen more commonly than vesicles at the time of presentation because of the frailty and thin walls of the vesicles. 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.
Genital herpes (female); outbreak of genital herpes affecting the vulva. Courtesy of Wikimedia Commons [SOA-AIDS Amsterdam] (https://commons.wikimedia.org/wiki/File:SOA-Herpes-genitalis-female.jpg).
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.
Genital herpes (male); vesicular lesions of HSV affecting the penis. Courtesy of Wikimedia Commons [SOA-AIDS Amsterdam] (https://commons.wikimedia.org/wiki/File:SOA-Herpes-genitalis-male.jpg).
In men and women, the ulcerative lesions persist from 4-15 days until encrusting and reepithelialization occur. The median duration of viral shedding is about 12 days.
Recurrent genital herpes
Recurrent infection implies infection by the same HSV type as the antibody in the serum. The major morbidity of genital herpes is due to its frequent reactivation rate. The duration of symptoms is usually shorter in recurrent infection than in primary infection.
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. HSV-2 seropositivity has been associated with viral shedding in the genital tract, even among individuals with no reported history or symptoms of genital herpes. [17] 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, 18] This feature 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, 9]
Herpes simplex virus type 1. Recurrent herpes is most often noted clinically as herpes labialis, with clustered vesicles (often coalescing) on the lip vermilion and often on the perioral skin. Recurrences generally occur in the same area each time, although their severity may vary. Courtesy of Sara Gordon, DDS.
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. [19]
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.
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). [20]
Herpes simplex virus type 1. Recurrent herpes is occasionally observed intraorally. Inside the oral cavity, recurrent herpes typically affects only keratinized tissues, such as the gingiva or the hard palate. Vesicles often break quickly, so the clinician may observe small clustered ulcers. Courtesy of Sheldon Mintz, DDS.
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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Herpes simplex virus type 1. Primary herpes can affect the lips, and the ruptured vesicles may appear as bleeding of the lips. Courtesy of A.K. ElGeneidy, DDS.
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Herpes simplex virus type 1. Recurrent herpes is most often noted clinically as herpes labialis, with clustered vesicles (often coalescing) on the lip vermilion and often on the perioral skin. Recurrences generally occur in the same area each time, although their severity may vary. Courtesy of Sara Gordon, DDS.
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This neonate displayed a maculopapular outbreak on his feet due to congenitally acquired herpes simplex virus infection. Courtesy of the CDC/Judith Faulk.
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Herpes simplex virus type 1. Recurrent herpes is occasionally observed intraorally. Inside the oral cavity, recurrent herpes typically affects only keratinized tissues, such as the gingiva or the hard palate. Vesicles often break quickly, so the clinician may observe small clustered ulcers. Courtesy of Sheldon Mintz, DDS.
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Herpetic whitlow in a young child who earlier had developed herpes gingivostomatitis. Courtesy of Wikimedia Commons [James Heilman, MD] (https://commons.wikimedia.org/w/index.php?search=Herpetic+whitlow+in+a+young+child&title=Special:MediaSearch&go=Go&type=image).
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Eczema herpeticum; cluster of blisters and punched out erosions of HSV in a child. Courtesy of Wikimedia Commons [Mohammad2018] (https://commons.wikimedia.org/wiki/File:Eczema_herpitcum.jpg).
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HSV encephalitis; coronal T2-weighted MRI showing increased intensity in the temporal lobes (arrow) in a 33-year-old female who presented with fever, confusion, agitation, and mutism and was diagnosed with HSV encephalitis. Courtesy of Wikimedia Commons [Dr Laughlin Dawes] (https://commons.wikimedia.org/wiki/File:Hsv_encephalitis.jpg).
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Genital herpes (female); outbreak of genital herpes affecting the vulva. Courtesy of Wikimedia Commons [SOA-AIDS Amsterdam] (https://commons.wikimedia.org/wiki/File:SOA-Herpes-genitalis-female.jpg).
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Genital herpes (male); vesicular lesions of HSV affecting the penis. Courtesy of Wikimedia Commons [SOA-AIDS Amsterdam] (https://commons.wikimedia.org/wiki/File:SOA-Herpes-genitalis-male.jpg).
