The herpes simplex virus (HSV) is a ubiquitous double-stranded DNA viral pathogen that can cause a wide variety of illnesses. Two types exist: type 1 (HSV-1) and type 2 (HSV-2). They are closely related, but differ in epidemiology. HSV-1 is transmitted primarily by contact with infected saliva, while HSV-2 is primarily transmitted sexually or from maternal-fetal inoculation from a maternal genital tract infection. HSV-1 is responsible for more than 90 percent of oral HSV lesions, with more than 85 percent of the world'ís population having serological evidence of previous HSV-1 exposure. (Dermatol Clin 2003;21:17.)
Acute (primary) herpetic gingivostomatitis refers to an oral herpetic outbreak in a previously seronegative person. The peak incidence of primary infection occurs between the ages of 1 and 5. (Clin Fam Pract 2003;5;589.) Typically these children are infected five to 10 days after mucocutaneous contact exposure to an infected person. It is not uncommon for this outbreak to go unnoticed by the patient; as many as 80 percent are asymptomatic.
Symptomatic infections can be characterized by significant morbidity and recurrence. Active disease, when it occurs, results in areas of painful erythema, edema, and hemorrhage that evolve to yellow vesicles with a red halo, then coalesce and rapidly ulcerate. Outbreaks can be associated with pharyngitis, fever, drooling (Clin Fam Pract 2003;5;589), malaise, and lymphadenopathy. Lesions can affect the lip, labial commissures, face, and the intraoral mucosa. Infection usually resolves within seven to 10 days in immunocompetent patients. (Dermatol Clin 2003;21:17.)
Following the primary infection, the virus migrates retrograde on the involved nerve axon to the sensory nerve ganglion where it lays dormant (latent phase). With herpetic gingivostomatitis, the trigeminal ganglia are most commonly involved. Reactivation results in recurrent infection with subsequent peripheral shedding of HSV. This occurs in approximately 40 percent of patients who harbor HSV-1 (J Oral Pathol Med 1997;26:441), and can be spontaneous or precipitated by many factors including fatigue, stress, menstruation, and ultraviolet light. HSV-2 recurrences in the oral mucosa are less common, typically milder, and have an abbreviated duration. (Dermatol Clin 2003;21:17.)
Reactivation of the virus in the trigeminal sensory ganglion gives rise to mild cutaneous and mucocutaneous disease known as recurrent herpes labialis, or more commonly, “cold sores” or “ìfever blisters.” These grouped lesions, typically three to five in an area less than 100 mm2 on an erythematous base, present on the cutaneous lip and vermilion starting as macules and progress to painful papulo-vesicles. These lesions ulcerate and crust over in 72 to 96 hours. Pain can be significant for the first four to five days of the eruption. Rarely are reactivations associated with intraoral ulcerations. (Clin Fam Pract 2003;5:589.)
In immunocompromised patients, reactivation can be atypical with more frequent outbreaks, more extensive and aggressive presentations, slow healing, and extreme pain. In these patients, intraoral HSV infection can occur at any location, making differentiation from other etiologies of recurrent aphthous ulcers almost impossible. (Dermatol Clin 2003;21:1.)
The differential diagnosis of recurrent aphthous ulcers is extensive. It includes but is not limited to trauma, recurrent aphthous stomatitis (commonly known as “canker sores”), syphilis, viral, zoster, erythema multiforme, cyclic neutropenia, acute necrotizing ulcerative gingivitis (Vincent's stomatitis), and oral cancer. In the ED, the diagnosis of herpetic gingivostomatitis is clinical, although numerous laboratory tests are available to aid in confirming the diagnosis. A Tzank smear specimen (obtained from scraping the ulcer base of an unroofed lesion) may demonstrate the typical features of an intracellular viral infection with a ground-glass appearance to the nuclear chromatin and multinucleated giant cells. Polymerase chain reaction, viral culture, direct immunofluorescence, in situ hybridization, antibody serology, histopathology, and biopsy all may be useful diagnostic adjuncts.
No cure currently exists for herpetic infections. The primary goal of therapy is largely supportive with an emphasis on decreasing pain, duration of symptoms, and viral shedding, and when possible, preventing outbreak. Antibiotics active against gram-positive bacteria are rarely given to prevent or treat bacterial superinfection of oral lesions. (Dermatol Clin 2003;21:17.)
Systemic antiviral therapy has been widely accepted as effective for primary herpetic gingivostomatitis. Systemic acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir) can be used to treat herpes simplex infections. Foscarnet (Foscavir) has been used to treat resistant cases. (Oral Dis 2006;12:254.)
Immunocompetent individuals with recurrent herpes labialis generally have full recovery in seven to 14 days, although treatment with antipyretics, analgesics, and oral anesthetics is often required. Mouth rinses containing topical anesthetic agents including viscous lidocaine (Xylocaine) or diphenhydramine (Benadryl) plus coating agents (magnesium-containing antacids) are helpful in relieving oral discomfort in severe herpetic gingivostomatitis.(Clin Dermatol 2000;18:619.) Oral fluid intake also must be encouraged to prevent dehydration.
Topical therapies have been found to be clinically efficacious in decreasing the mean time to healing and the duration of symptoms of recurrent herpes labialis including acyclovir 5% cream and ointment, penciclovir (Denavir), and over-the-counter docosanol 10% cream (Abreva). These topical agents were compared recently in an animal model, which found the efficacy of penciclovir to be greater than acyclovir cream, which was greater than or equal to that of acyclovir ointment. The efficacy of all compared agents was superior to that of docosanol cream. (Arch Dermatol 2001;137:1153.)
Recurrent herpes labialis infection rarely merits systemic therapy. Systemic acyclovir may be effective in reducing the duration of symptoms of recurrent HSV-1 infection, but the optimal timing and dose of the treatment are uncertain. (Oral Dis 2006;12:254.) Valacyclovir also may be useful. Oral acyclovir has been shown to reduce the duration of symptoms and infectivity in children. (Brit Med J 1997;314:1800.)
Preliminary findings suggest that treating lesions with 1072-nm waveband light may decrease healing time significantly compared with topical acyclovir treatment five times daily. German investigators found a combination of rhubarb-sage cream to be almost as effective at reducing healing time and reducing pain as acyclovir cream. Zinc oxide/glycine combination cream reduces blistering, soreness, itching, tingling, and healing times when compared with placebo. (Clin Fam Pract 2003;5;589.)
In immunocompromised HIV-infected patients with severe recurrent herpetic gingivostomatitis, acyclovir and famciclovir may be of benefit for acute treatment. (AIDS 2000;14:1211.) Typically, patients are treated with oral acyclovir therapy (200 mg five times a day for the first three to five days after samples for laboratory confirmation of HSV are obtained). If the response is poor, the dose may be increased to 800 mg five times a day. If there is no notable clinical improvement after five to seven days, it is unlikely lesions will respond to intravenous acyclovir (or chemically and structurally related drugs such as valacyclovir or famciclovir), thus an alternative regimen should be utilized. (Oral Dis 2006;12:254.)
There is evidence that prophylactic oral acyclovir may reduce the frequency and severity of recurrent oral herpetic infections in immunocompromised patients, but the optimal timing and duration of treatment is uncertain and can vary in different situations. (Oral Dis 2006;12:254.) Similar to acyclovir, famciclovir is equally effective in preventing new lesion formation, but it has the convenience of less frequent dosing. Data on the use of prophylactic acyclovir for immunocompetent patients have been mixed. (Clin Fam Pract 2003;5;589.) Protection of the lips from ultraviolet exposure with sunscreen also is beneficial in preventing oral herpetic outbreaks. (Lancet 1991;338:1419.)
Most patients with mild herpetic gingivostomatitis (also known as recurrent herpes labialis) exacerbations can be sent home, but the clinician should maintain a low threshold to admit patients with severe and extensive mucocutaneous involvement, those who are immunocompromised or elderly, pediatric patients with primary herpetic gingivostomatitis, and those requiring intravenous pain control or hydration. All patients should be counseled about the risk of transmission during viral shedding.
This patient was admitted to the hospital and started on intravenous acyclovir. Serology was positive for both HSV-1 and HSV-2 antibodies. He left against medical advise during the first hospital day, and was lost to follow-up.