Herpes Labialis

What is herpes labialis?

Herpes labialis is an infection of the lips or "perioral" (around the mouth) area. The primary infection is usually asymptomatic, however, it can also present itself as HSV gingivostomatitis (inflammation of the gum). After the primary infection, latency is established. Reactivation can occur as lesions or sores around the mouth area called "cold sores" or "fever blisters". Recurrences are generally mild and self-limited, but the sores can be unsightly and can cause significant discomfort or embarrassment.

What causes herpes labialis?

Herpes labialis (fever blisters, cold sores) can be caused by either HSV-1 or HSV-2. While the primary (first episode) infections with HSV-1 or HSV-2 do occur, recurrences are generally the result of HSV-1 infection. Oral recurrences with HSV-2 are very rare.

Who gets this infection?

The first episode of HSV-1 infection generally occurs in children and young adults and is usually asymptomatic. HSV-1 infections are one of the most common infections throughout the world.

How many people have this infection?

HSV-1 infections are acquired by almost all people in all nations and countries. In underdeveloped countries seroconversion to HSV-1 occurs in up to 33% of children by 5 years of age and prevalence rises to 70 - 80% by adolescence. By contrast in developed countries, middle and upper-class individuals acquire infection later in life. Seroprevalence of HSV-1 can be as low as 20% in children younger than 5 years of age and in adolescents. The acquisition rises between 20 and 40 years to a prevalence of 40 - 60%.

In the United States, approximately 130 million individuals over the age of 12 are infected with HSV-1. Evidence suggests that seroprevalence of HSV-1 may be declining in children and adolescents probably due to less crowding and better hygiene. This shift in HSV-1 seroprevalence has the paradoxical effect of increasing the risk of newborn HSV-1 infection. Some women who have not previously acquired HSV-1 do so in pregnancy. Genital herpes due to HSV-1 can be transmitted during oral sex if the partner is actively shedding HSV-1 from the mouth.

What are the symptoms of herpes labialis?

First Episode
Most people acquire HSV-1 asymptomatically. Only a few actually develop symptoms when they acquire the infection. For those who have symptomatic first episodes, the most common signs are gingivostomatitis and pharyngitis (inflammation of lower throat). Lesions outside the mouth can also occur.

Clinical symptoms and signs of first episodes, which include fever, malaise, myalgias, inability to eat, irritability, and cervical adenopathy, may last from 3 to 14 days. Fever lasting from 2 to 7 days and swollen lymph nodes in the neck are common. Lesions may involve the hard and soft palate, gingival, tongue, lip, and facial area. HSV-1 infection of the pharynx usually results in fluid filled or ulcerative lesions of the lower pharynx and/or tonsils. Lesions on the tongue, inside the cheek, or gums may occur later in the course in one-third of cases. The lesions rapidly rupture, become ulcerative, and last approximately 12 days with the number of vesicles peaking at about 6 days and gradually diminishing. The lesions can be very painful and make swallowing uncomfortable, leading to other clinical symptoms of drooling or difficulties in drinking and eating. Dehydration secondary to poor fluid intake leads to hospitalization in a small percentage of affected children.

What happens when it recurs?

Recurrent Episodes
Herpes labialis is the most frequent clinical sign of reactivation of HSV infection. As described in What is Herpes?, reactivation from the nerve roots may be associated with asymptomatic virus excretion in the saliva, development of mucosal ulcerations inside the mouth, or herpetic ulcerations of the edge of the lip or external facial skin. About 10 to 15% of those having a tooth pulled develop oral-labial HSV infection an average of 3 days after that procedure.

Herpes labialis is often confused with another oral condition, aphthous ulcers or "canker sores". Aphthous ulcers recur sporadically inside the mouth or on the tongue. They are caused by a bacterium and last a week or two. Unlike cold sores, which tend to reappear in the same place, aphthous ulcers can occur in different places within the mouth.

Once latency is established, about 20 - 40% of people will have symptomatic recurrences. Although recurrent infection is less severe than a primary episode, lesions can be painful and embarrassing. The psychological impact of having a lesion on the face — particularly if the recurrences are frequent — can be serious.

What triggers a recurrence?

Several things may precipitate a recurrence and are specific to the individual person. Exposure to UV light, febrile illnesses, stress, premenstrual tension, and surgical procedures such as dental or neural surgery, lip tattooing, or dermabrasion are a few of the more common triggers.

Avoidance of these triggers can reduce your risk of recurrence. For example, if your lesions are subject to reactivation due to exposure to UV light, the use of sunscreens with SPF of 15 or greater may be helpful when you are going to the beach. However, sun screens are not as helpful when skiing. This is probably because in addition to UV light exposure, there is a great deal of wind and cold that are increasing skin trauma. In this case you may want to take prophylactic oral acyclovir while skiing.

How is herpes labialis transmitted to others?

Herpes labialis is spread through the direct contact of skin or mucus membranes with lesions or oral secretions of an infected person. Risk of transmission often increases in day care settings due to large numbers of children who are in close proximity. Most of the transmission in these settings is believed to be asymptomatic. Transmission in households is believed to be from kissing, though it is good to avoid sharing cups, eating utensils, wash cloths, etc. when one has a visible sore.

The infection is transmitted when there is virus present. The highest chance of virus being present is when there are visible lesions. The amount of virus present is highest within the first eight hours of lesion development and diminishes as the lesions mature. Other things that might increase the amount of virus that is present are colds,oral surgery, and facial cosmetic surgery.

As with genital herpes, people can shed virus without any noticeable signs or symptoms of disease. Occasional, asymptomatic shedding may occur in 2 - 9% of individuals with herpes labialis. To avoid transmission of HSV-1 infections people with active lesions (fever blisters or cold sores) should avoid kissing others and having oral/genital sex.

How do you diagnose herpes labialis?

Most Herpes labialis cases are diagnosed clinically. Most episodes are preceded by a prodromal phase that is characterized by pain, burning, itching, and erythema, lasting about six hours. These symptoms are usually followed by lesions on or near the lips. Over the next 72-96 hours these papules progress to vesicles (blisters) and then ulcers. As the lesions heal they form hard crusts. The lesions are generally completely healed by 8 to 10 days. Pain can be severe at the start of the infection and resolves over the next 4 - 5 days.

Most lesions occur on the lips. However, lesions can also occur on the nose, cheeks, or chin. Lesions occurring in the oral cavity or face are less common. Intraoral lesions are hard to locate and are difficult to distinguish from apthous ulcers or canker sores.

About 25% of all episodes do not progress beyond the papule stage. These are called "aborted" episodes. About one-half of these do not progress beyond the prodromal stage.

Are there any treatments for herpes labialis?

Primary Infection: All children diagnosed with HSV gingivostomatitis should be treated with oral acyclovir 15mg/kg (to a maximum dose of 200mg) five times a day for five days. No studies have been done to determine the best dose for adults.

Recurrent infection: Two approaches to treatment may be taken: 1) Episodic treatment is used when symptoms begin. 2) Prophylactic treatment requires use of the medicine before symptoms occur to prevent or lessen the impact of an episode. Both approaches are recommended only if the medicine used has antiviral activity.

Most episodes of herpes labialis are preceded by a prodromic phase. Prodromes may consist of signs or symptoms such as tingling, itching, or redness. These can last for up to 24 hours before lesion development. It is best to begin therapy at the earliest sign or symptom, preferably before skin disruption. However, regardless of the stage of disease, antiviral therapy may be beneficial in shortening the episode.

Topical Therapies: Many types of approaches to topical therapy of cold sores are available. These are both presented and over the counter topical therapies for cold sores that are effective. Both Zovirax® Cream 5% (applied five times a day for four days) (Biovail) and Denavir® (applied every two hours during the day for four days) (Novartis) are effective for treatment of herpes labialis episodes when the medicine is applied as soon as symptoms are first recognized. These antiviral treatments work to inhibit HSV replication in the lesion and have been shown to decrease healing times by approximately half a day. Additionally, both products significantly reduce the duration of pain associated with herpes labialis. Oftentimes, the reduction of pain and the moistening of the crust have a soothing effect. When compared to each other, Zovirax Cream and Denavir have similar effects. These creams can be prescribed by your health care provider.

Many over-the-counter products are available and sold as effective therapies for cold sores. However, only two (Abreva and Novitra; see below) have shown efficacy in controlled clinical trial in reducing healing time and duration of pain. Only Abreva has received FDA approval for OTC (over-the-counter) marketing without a prescription. All others are palliative (soothing) at best.

Abreva® (GlaxoSmith Kline) is the only over-the-counter (OTC) product that has had demonstrated efficacy in a controlled clinical trial and has been approval fromthe FDA. Abreva is applied five times a day until lesions are healed. Another product, Novitra®, is applied every two hours until healing occurs or up to 21 days. Novitra was shown to have efficacy in a controlled clinical trial. It is not clear why it does not have FDA approval. Since these products have no antiviral activity, the effect is probably due to anti-inflammatory rather than anti-viral activity.

Treatments that are not recommended. Novitra®, was shown to have efficacy in a controlled clinical trial. It is applied every two hours until healing occurs or up to 21 days. It is not clear why it does not have FDA approval. Since these products have no antiviral activity, the effect is probably due to anti-inflammatory rather than anti-viral activity. Other products that you will see advertised in your local pharmacy have no proven benefit in the management of herpes labialis. These products would only be palliative at best. They have no therapeutic benefit. Unfortunately, the regulations that govern OTC advertising are much less restrictive that those for prescription products. OTC products are allowed a broad interpretation of claims. At most they might act as a sun screen (Herpecin®) or as a palliative to moisten dry skin or dry moist skin (Champho-Phenique®). Others are likely to cause stinging or numbness. Some even capitalize on a trusted product name (Neosporin CT®). This product has no relationship to the well studied and trusted antibiotic, Neosporin®, that has been available for years. Some of the more common OTC products are listed in the following table.

Oral Therapy: Three drugs have shown efficacy in the treatment of herpes labialis but only one (Valtrex®) has received licensure for this indication. Valtrex® (2 Grams twice a day for one day) has been shown to speed healing and shorten pain of recurrent episodes. Other products that have shown an effect on healing times in clinical trials are Zovirax® Capsules (200-400 mg five times a day for five days) and Famvir® (500 mg three times a day for five days).

Prophylactic Therapy — Short-term, situational to prevent an outbreak:

Topical Therapy:
In one study, Zovirax® Cream 5% (Biovail) showed a protective effect when applied 12 hours before skiing. In this study, application of the cream reduced lesion development by 50% when compared to placebo. It is likely that potential benefit could also be gained if used prior to sunbathing.

Sun screens may be helpful if used prior to UV light exposure (before sun exposure). These could be used prior to sunbathing. However, they are unlikely to be helpful if you are also having a significant wind exposure, e.g. skiing.

Oral therapy:
It is unclear whether or not Zovirax® Capsules will prevent recurrences of herpes labialis when taken prior to known triggers. In one trial, those people receiving Zovirax (400mg twice a day initiated 12 hours before skiing and continued for seven days) experienced significantly fewer reactivations (7% versus 26%). However, a subsequent study of a higher dose did not show a beneficial effect.

Prophylactic Therapy — Short-term

Prophylactic Therapy — Continuous Suppressive Therapy

Topical Therapy:
No topical product has shown efficacy as long term suppressive therapy. Clinical trials conducted to date have been small; however, no efficacy was noted.

Oral Therapy:
Both Valtrex® (500mg once a day) and Zovirax® (400 mg twice a day) have been shown to prevent recurrences when taken daily. This should be considered in people who have frequent recurrences.