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Primary Herpes Simplex Virus (HSV) Infection

Aug 17, 2007
Primary Herpes Simplex (HSV-I) type 1 produces the most common viral infection in the oral cavity. It most often occurs in children under 6 years of age but can involve older patients. In most children primary infection is sub-clinical (without clinical signs or symptoms); about 13% of children have had symptomatic herpes by age 9.

The herpes simplex viruses are virtually ubiquitous in the general population; over 90% of adults have antibodies to herpes simplex virus by the fourth decade of life. Once an individual is infected, the virus spreads to regional mass of nerve tissue, ganglia (e.g., the trigeminal ganglion), where it remains latent but can be reactivated whenever conditions are appropriate.

The causes and the course of the disease:

Both herpes simplex types 1 and 2 may cause both orofacial and genital infections, but HSV-I is more frequently responsible for lesions in and about the mouth ranging from the relatively trivial cold sore to a vesiculoinflammatory (having small blisterlike elevations on the skin with fluid in them) eruption. These lesions typically involves large areas of the oral mucosa, the moist surface tissues that line the mouth, throat and lips. This condition is called gingivostomatitis.

In addition, herpes simplex virus infection may involve the membranes of the eye, causing the keratoconjunctivitis. In newborn infants or immuno-compromised (with depressed immune system) adults, the infection may involve visceral organs (e.g., lungs, liver) or produce encephalitis (inflammation of the brain) or fatal disseminated disease.

Recurrent herpetic infections develop in about one third of those patients who have had a primary infection. Herpes labialis is the most frequent type of recurrent infection. It usually is seen as a cluster of vesicles appearing around the lips after a systemic illness or other stress-fill situation. Ultraviolet light and mechanical stimuli may also produce recurrences.

The clinical features

(1) Herpes Labialis:

The "cold sore" or "fever blister" as is well known to all, constitutes a vesicular lesion usually located around mucosal orifices such as the lips and noses. Often several lesions appear simultaneously or in quick succession. There is frequently a history of previous respiratory infection or fever, exposure to sunlight or cold, or trauma to the area, but whether these influences in fact activate the virus remains unclear.

The vesicular lesion begins with a focus of intracellular and intercellular edema followed by ballooning degeneration of epidermal cells and acantholysis (separation of cells) with the formation of an intraepithelial vesicle (blister). Individual epidermal cells in the margins of the vesicle or lying free within the fluid develop intranuclear inclusions composed of live and dead virions. Sometimes several cells fuse to produce polykaryons or giant cells that can be identified in smears of blister fluid (Tzanck preparations). The vesicles are prone to burst to produce superficial ulcerations, and in most cases, in the course of a few days are covered with a fibrinous coagulum and progressively heal.

(2) Herpetic Gingivostomatitis:

Primary herpetic gingivostomatitis is a more florid form of herpetic infection of the oral cavity that occurs in the compromised host (debilitation, impaired immunity, immunosuppressive therapy, and in the very young who lack antibodies). The lips and gingival and buccal mucosa are involved but sometimes also the tongue and retropharynx. The individual lesions may begin as vesicles but may extend into the mucosa and deep cutaneous layers, favoring systemic dissemination. Coalescence of the lesions leads to denudation of large areas of the mucosa. There is a commensurate greater inflammatory reaction and consequent edema and erythema.

The primary episode of herpetic gingivostomatitis is characterized by constitutional symptoms such as malaise, fever and regional lymphadenopathy. Acute ulcerative gingivostomatitis occurs as a result of virus replication in the affected tissues. Vesicular eruptions may occur throughout the mouth. The gingivae are red and swollen and bleed readily. They may have a mottled appearance in the maxillary areas. Touching them or attempting to consume food causes severe pain.

(3) Herpetic Whitlow:

Herpetic infection of the digits occurs through a break in the skin and results from localized virus replication which causes swelling, redness, and tenderness with subsequent vesiculation. Healing follows in 2 weeks; as in other HSV infections, latency and periodic reactivations are common.

The differential diagnosis:

There are two types of herpes simplex virus that cause disease in humans. The type 1 virus is primarily associated with infections of the skin and oral mucous membrane, and type 2 with infections of the genitalia (although the converse can and does occur).

The diagnosis of primary herpetic gingivostomatitis is usually made on a clinical basis. The patient has a number of vesicles or small painful ulcers throughout the oral cavity. A history of systemic signs and symptoms of a viral illness helps to establish the diagnosis. The differential diagnosis of primary herpetic gingivostomatitis has been reviewed in the differential diagnosis of recurrent aphthous stomatitis. In addition, hand-foot-mouth disease (viral etiology) needs to be considered because multiple pinpoint oral vesicles and ulcers, as well as fever, are common signs. The absence of lesions on the palms and soles eliminates hand-foot-mouth disease from consideration. Herpangina (coxsackievirus) can generally he identified by the limited distribution of the small vesicles and ulcers to the soft palate and oropharvnx.

The recommended treatment:

Confirmation of the viral infection by lahoratory methods is available but not routinely used. The virus may be isolated in tissue culture if fluid can be obtained from an intact vesicle. Primary infections are associated with an increase in antibody titer, and paired acute and convalescent sera may be studied.

There is no specific treatment for primary herpetic gingivostomatitis. Acvclovir (Zovirax) is effective in the management of initial herpes genitalis. It is also useful in treating non-lifethreatening mucocutaneous herpes simplex virus infections in immunocompromised patients (Myers et al., 1982; Whitley et al., 1982). In these patients a decrease in the duration .of viral shedding has been reported. There is no reported clinical evidence of benefit in treating herpes labialis in non-immunocompromised patients.

The usual supportive measures for an acute viral infection should be instituted. These include maintenance of proper oral hygiene, adequate fluid intake to prevent dehydration, and the use of systemic analgesics for control of pain. Antipyretic agents are also prescribed when fever is a symptom. In severe cases it may be necessary to use a topical anesthetic mouth rinse such as viscous lidocaine or elixir of diphenhyclramine. The patient is often able to tolerate cold liquids, and they may aid in preventing dehydration. Secondary bacterial infection of the many small punctate ulcers invariably is a major contributor to the pain after the vesicles rupture.

Herpetic Whitlow is a recognized occupational hazard of dental personnel and may be contracted through treatment of patients with oral herpetic lesions. The dentist, hygienist, or assistant in turn, may transmit this infection to other patients. To prevent this infection, gloves should be used routinely when examining or treating patients.
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