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Acyclovir for Treating Primary Herpetic Gingivostomatitis

7 November 2008

Acyclovir for Treating Primary Herpetic Gingivostomatitis
Primary herpetic gingivostomatitis (PHG) is an infection of the oral cavity which is caused by the herpes simplex virus (HSV). It is highly contagious, typically affects children but can also occur in adults, and has a high rate of recurrence of infection .

Symptoms may vary widely from mild discomfort to life-threatening encephalitis. Only about 5% to 10% of patients initially infected with the herpes simplex virus develop clinical lesions. This is referred to as primary herpetic gingivostomatitis.

Many patients may remain undiagnosed because they are either asymptomatic or have mild symptoms . Ninety per cent of Americans are said to have HSV-1 serum antibodies. The peak periods of PHG incidence are between the ages of 6 months and 5 years, and in young adults who are in their early 20s.

The herpes simplex virus is a double-stranded DNA virus of which the HSV-1 type is responsible for oral, facial and ocular infections including primary herpetic gingivostomatitis. Although HSV-2 is primarily responsible for most genital and cutaneous lower body herpetic lesions, it can also be the cause of primary herpetic gingivostomatitis.

Although the virus is short lived on external surfaces it can readily disrupt the integrity of skin or mucous membranes and viral replication occurs as soon as it penetrates the epithelial cell. It is at a later stage that the virus travels along the sensory nerve endings to the corresponding nerve ganglion i.e. the trigeminal ganglion, where it enters a latent phase and can remain dormant until it is reactivated either spontaneously or by one or another of a number of stimulants e.g. infection, ultraviolet light, fever, cold.

As the infection is highly contagious, most patients acquire it through direct contact e.g. skin or via infected secretions e.g. saliva. It can spread rapidly in a closed community setting such as a daycare nursery or orphanage. Therefore, factors such as location and socio-economic status can influence the rate of HSV-1 infection and it has been noted that individuals in developing countries and from lower socio-economic groups become HSV-1 seropositive at an earlier age than individuals from developed countries.

PHG is characterised by a sudden onset and with the severity of symptoms related to the virulence of the HSV and the host's immune response. Non-specific symptoms may include cervical lymphadenopathy, malaise and low grade fever, and can occur in the absence of any discrete clinical lesions.

The general course of PHG infection is 10 to 14 days which is usually preceded by an incubation period of 1 to 26 days.

Primary herpetic gingivostomatitis can include oral as well as extraoral lesions, swollen and bleeding gums, and symptoms such as pain, fever, irritability, malaise, headache and upper respiratory tract infection.

The oral lesions in PHG may start as vesicles on the tongue and the buccal and gingival mucosa, and which rapidly rupture to become ulcers. The ulcers, which are usually 1 to 3 mm in size, may subsequently enlarge to form a large ulcerated area covered by a yellowish-grey membrane. In some patients, especially adults, the gingivae (gums) may also become swollen. Healing generally occurs without scarring.

During the acute phase of PHG many children may refuse to eat or drink because of the discomfort and pain from these lesions and consequently become rapidly dehydrated. Extraoral lesions (herpes labialis), which appear as erythematous papules on the vermilion border and adjacent skin of the lips, may accompany PHG.

Complications are rare but do occur and usually as a result of viral shedding, and it is at this stage that HSV infection becomes readily transmittable. During this phase with its high risk of direct transmission, eye infections (ocular herpes or herpetic keratoconjunctivitis) and infections of the digits (herpetic whitlow) are not infrequent complications. After the primary infection, the virus may become dormant but can be readily reactivated producing episodic bouts of recurrent infection which are generally considered to be less severe than the primary infection.

The diagnosis is usually made by clinical presentation and history. In addition, the diagnosis may be confirmed via laboratory tests: serological assays , the Tzanck test and immunofluorescence, but the culture of viral isolates is still considered to be the gold standard.

The differential diagnosis of PHG includes acute necrotizing ulcerative gingivitis, herpangina, aphthous stomatitis, candidiasis of the mouth, Steven-Johnson syndrome and hand, foot and mouth disease.

Individuals with symptoms such as pain, fever, and dehydration may seek treatment including rehydration, analgesics and oral lavage. Systemic analgesics (acetaminophen) may be adequate to manage the associated pain but topical applications of diphenhydramine and viscous lidocaine are also frequently prescribed.

Reduction of viral replication by using antivirals may shorten the acute phase of the illness, relieve symptoms, stop the virus from going into the latent phase and possibly prevent future recurrence . A known selective inhibitor of replicating HSV is acyclovir which is widely used for different forms of HSV infections.

Acyclovir, in either oral or topical form, is used fairly routinely for HSV infections e.g. herpes encephalitis, neonatal herpes, primary herpes genitalis and recurrent herpes labialis. One of the limitations of acyclovir is its poor gastrointestinal absorption and bioavailability and therefore derivatives, e.g. valacyclovir and famciclovir, have been developed with an apparently increased bioavailability but these are not currently available as paediatric suspensions.

Original article by: Nasser M et al
Reference: Acyclovir for treating primary herpetic gingivostomatitis.
Cochrane Database of Systematic Reviews 2008, Issue 4. Source: Cochrane Library (via NELM)
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