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Herpes labialis
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Herpes labialis (also known as ‘cold sores’) is characterized by recurrent vesicular eruptions primarily on the lips and perioral skin. The condition is contagious, can cause significant discomfort/pain, and can have an adverse effect on quality of life. Herpes labialis is caused by reactivation of herpes simplex virus type 1 (HSV-1). After a primary infection, HSV-1 establishes chronic latency within the trigeminal ganglion. When an appropriate trigger occurs, the virus reactivates, replicates in the trigeminal ganglion, descends along the sensory nerve axon to the perioral epithelium, and results in herpes labialis. A prodrome including irritation, pruritus, tingling, numbness, burning, and pain may occur at the site of future lesion development.
Management Strategy
Antiviral therapy shortens the duration of discomfort/pain, hastens healing, and reduces viral shedding, thereby reducing dissemination of HSV. Treatment should be initiated ideally in the prodromal stage and no later than 48 hours from the onset of lesions to obtain maximal clinical effect. Oral antiviral agents for herpes labialis include aciclovir, famciclovir, and valaciclovir and they are superior to topical antiviral agents. The metabolites of these nucleoside derivatives interfere with the synthesis of viral DNA. For episodic treatment, the recommended oral dose of aciclovir for children is 15 mg/kg (maximum 200 mg) and that for adults 400 mg five times a day for 5 days. Oral famciclovir and valaciclovir are alternate options for individuals ≥18 years and ≥12 years, respectively. Famciclovir and valaciclovir have greater oral bioavailability and are better absorbed than aciclovir and require less frequent dosing, but are more expensive. The recommended oral dose of famciclovir is 750 mg twice a day or a single dose of 1500 mg for 1 day and that of valaciclovir is 2000 mg twice a day for 1 day.
Topical antiviral agents such as 5% aciclovir cream/ointment alone or in combination with 1% hydrocortisone and 1% penciclovir cream are also available for the episodic treatment of herpes labialis. Topical aciclovir requires applications five times a day whereas penciclovir requires applications nine times a day. The duration of treatment depends on the response to therapy. Topical aciclovir mucoadhesive buccal tablet once a day has also been shown to be effective.
Topical application of docosanol 10% cream five times daily has also been shown to be effective.
The use of intravenous aciclovir should be considered in immunocompromised patients and those with severe infections. The recommended dose of aciclovir is 5 mg/kg infused over an hour, delivered every 8 hours. The duration of treatment depends on the severity of symptoms and response to treatment.
Avoidance of known triggers such as emotional stress and ultraviolet radiation may diminish the number of recurrences. In patients with a history of solar-induced reactivation of herpes labialis, avoidance of sun exposure especially during hours of peak ultraviolet intensity (11 am–4 pm), regular use of broad-spectrum sunscreens, and wearing of protective wide-brimmed hats should be considered.
Chronic suppressive therapy with aciclovir or valaciclovir should be considered for patients with severe or frequent (six or more episodes per year) recurrences. The recommended oral dose of aciclovir is 400 mg 2–4 times a day and that of valaciclovir is 500 mg daily or twice a day. There is no data on the use of famciclovir for this purpose.
Other treatment modalities for the management and prevention of recurrent herpes labialis include laser therapy and photodynamic therapy.
Specific Investigations
The diagnosis is mainly clinical. Laboratory investigations should be considered if the diagnosis is in doubt.
Efficacy and safety of nucleoside antiviral drugs for treatment of recurrent herpes labialis: a systematic review and meta-analysis
Chen F, Xu H, Liu J, et al. J Oral Pathol Med 2017; 46: 561–8.
A meta-analysis of 25 randomized controlled trials (RCTs) ( n = 8453 patients) showed that both topical and systemic nucleoside antiviral agents decreased time to healing of all herpes labialis lesions and increased the percentage of aborted lesions. Oral antiviral agents were superior to topical antiviral agents and required less frequent applications. Oral valaciclovir was more effective than aciclovir in reducing the time of healing of all lesions and the time of resolution of pain.
Single-dose, patient-initiated famciclovir: a randomized, double-blind, placebo-controlled trial for episodic treatment of herpes labialis
Spruance SL, Bodsworth N, Resnick H, et al. J Am Acad Dermatol 2006; 55: 47–53.
An RCT for episodic treatment of herpes labialis ( n = 701) showed that single-dose famciclovir was as efficacious as single-day, twice-daily dosing in time to healing of herpes labialis lesions and was superior compared with placebo.
Oral acyclovir and herpes labialis: a randomized, double-blind, placebo-controlled study
Raborn GW, McGaw WT, Grace M, et al. J Am Dent Assoc 1987; 115: 38–42.
An RCT ( n = 149) showed oral aciclovir, 200 mg five times per day for 5 days, showed a significant antiviral effect in the treatment of herpes labialis, but that higher doses or a loading dose could improve its efficacy.
Treatment of recurrent herpes simplex labialis with oral acyclovir
Spruance SL, Stewart JC, Rowe NH, et al. J Infect Dis 1990; 161: 185–90.
In an RCT ( n = 174), patients treated with aciclovir 400 mg five times a day for 5 days had a decreased frequency of HSV culture-positive lesions, decreased duration of pain, and decreased duration of lesions compared with placebo.
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