Treatment of Recurrent Herpes Labialis

Cold sores, also known as herpes simplex labialis (HSL) affect millions of Americans. While evidence of serologic infection with herpes simplex virus type 1 (HSV- 1) approaches 80% in the general adult population, only about 30% of people have clinically apparent outbreaks. The painful cluster of vesicles on an erythematous base is caused by the herpes simplex virus. Herpes labialis is the most common infection caused by HSV-1, whereas genital herpes is usually caused by herpes simplex virus type 2 (HSV-2). However, oral/ genital sexual relations can allow the viruses to cross-infect; consequently, HSV-2 is responsible for herpes simplex labialis in 10-15% of cases. Intimate contact between a person who is actively shedding the virus (or with body fluids containing the virus) and an individual who is susceptible (who lacks antibodies against the virus) is necessary for HSV infection to occur.¹

The contact must involve abraded skin or mucous membranes. HSV invades the epidermal and dermal cells and travels to the sensory neurons (dorsal root ganglion) where latency is established. The virus replicates in the neurons, leading to recurrent outbreaks. The outbreaks are often induced by exposure to ultraviolet light (sunlight and/or tanning beds), stress, immunosuppression, the common cold, fatigue, fever (hence the term “cold sore” or “fever blister”), overexposure to the wind, extremes in temperature, menstrual periods, pregnancy, dental work, or lip trauma. Perioral laser resurfacing or injection of perioral botulinum toxin or fillers can stimulate an outbreak. Transmission of the virus can occur during primary infection, during subsequent recurrent infections, and even during periods of asymptomatic viral shedding.

At present, there is no cure for HSL, so theoretically, once contracted, the infection remains for life. The initial HSV-1 infection is often asymptomatic and may not be noticed, or a fever may be the only symptom. When perioral lesions do occur with the primary infection, the initial outbreak is often the most severe; recurrences are typically more attenuated as a result of antibody production.² Approximately one-third of patients who experience the initial HSV-1 infection go on to have recurrent herpes labialis (RHL). Most patients with RHL have less than two episodes per year but 5-10% experience six or more recurrences per year.³ The pain, embarrassment, and temporary disfigurement of herpes lesions can be reduced by taking medication at the first sign of prodromal symptoms, such as itching, tingling, and burning, or by taking daily suppressive therapy. Most HSV infections are self-limited. However, antiviral therapy shortens the course of symptoms and may prevent transmission and dissemination.

Commercially available topical treatments are much less effective than IV or oral systemic therapy. All treatments are most effective if used at the first onset of symptoms.

N-docosanol is a 22-carbon alcohol that has been FDA approved as an OTC agent for treating RHL. Applying the cream five times per day prevents fusion between plasma membranes and the HSV-1 virus envelope, reducing the risk of intracellular entry with subsequent viral replication. Ideally, docosanol is applied during the prodromal stage, but it is still useful, even at a later stage at shortening healing time and duration of symptoms.⁴

Acyclovir cream, FDA approved for RHL, has been shown to reduce lesion healing time by 0.5-0.6 days and the duration of pain by 0.3-0.4 days.⁵

Penciclovir cream, FDA approved for RHL, has been shown to reduce healing time in two studies by 0.7 and by two days, respectively, when compared with placebo controls.^6,7 When compared directly with topical acyclovir cream in a randomized controlled trial with 124 subjects in each treatment group, there was no statistical difference between the two agents with respect to clinical healing time of herpetic lesions.²

This combination cream is FDA approved to treat RHL. In one study of 120 subjects with lesions of HSL, 50 subjects received the treatment combination cream and 70 subjects received the