US Pharm
. 2015;40(4):8-12.

After 27 years with U.S. Pharmacist, Dr. Steve Pray is retiring from this column. Over the years, he has covered everything in the nonprescription market, from Rx-to-OTC switches to the emergence of behind-the-counter products to pain relievers, allergy medications, and beyond. His contributions will be greatly missed.

Pharmacists counsel patients about a host of oral conditions, such as xerostomia, sore mouth, teething, toothache, canker sores, and herpes simplex labialis. The latter condition, also known as fever blisters or cold sores, is particularly painful, and several nonprescription products may provide relief.

Prevalence of Herpes Simplex Labialis

Herpes simplex labialis is not a reportable disease, so exact numbers of persons affected are not available. However, the incidence is thought to be 1.6 per thousand people annually, and the prevalence is estimated to be 2.5 patients per thousand, up to as many as 20% to 40% of adults.1,2 Once it is contracted, the virus cannot be eliminated, so the percentage of those carrying it rises as the average age of the group being sampled increases. The National Institutes of Health (NIH) states that the majority of residents of the United States are infected with the virus by the age of 20 years.3

Etiology of Herpes Simplex Labialis

The most common cause of herpes simplex labialis is the type 1 herpes simplex virus, abbreviated as HSV-1.3 HSV-1 is the causal agent in more than 95% of patients who experience recurrent fever blisters.4 The remainder of cases are caused by HSV type 2 (HSV-2), the infective agent associated with genital herpes. Having oral sex with a person infected with HSV-2 can result in HSV-2 herpes simplex labialis.

Manifestations of Herpes Simplex Labialis

Herpes simplex labialis outbreaks generally proceed in several predictable stages.5 For a large number of patients, the first stage is the prodrome. In this stage, the patient experiences a set of problems that precede the actual appearance of the lesion. Prodromal symptoms include any or all of the following: 1) pruritus of the lips or of the skin around the mouth; 2) a tingling sensation near the lips and/or mouth area; 3) burning near the lips or the perioral region; 4) inflammation or erythema; and 5) hypersensitivity of the area.3,5 The prodromal symptoms are often located at the exact spot where the lesion is shortly due to erupt.

The most common site for herpes simplex labialis is found in the name—labialis, referring to the lip. More specifically, the area is the mucocutaneous junction where intraoral tissues abut the upper and lower lips, an area also referred to as the vermilion border.3,6 Patients with recurrent herpes simplex labialis usually report that the prodrome and lesion occur at the same site from episode to episode. Occasionally, they break out on the skin surrounding the nose or cheek, and intraoral tissues such as the gingiva may be affected.3

The prodromal stage of herpes simplex labialis may also include general symptoms, such as sore throat, fever, swollen lymph nodes, malaise, and odynophagia (i.e., pain when swallowing).3,5 The prodrome can last for as long as 1 to 2 days.

The prodromal stage ceases with the first visible manifestation of herpes simplex labialis, blisters filled with clear, yellowish fluid. The first crop can be somewhat scattered, but additional blisters often continue to appear, enlarging the area of involvement as individual lesions coalesce. Eventually, the lip appears disfigured due to the extent of the area affected. The area is exquisitely painful and pruritic.

The blisters remain intact for 2 days, following which they begin to spontaneously rupture. The area beneath ruptured blisters is an open, erythematous, weeping wound. The fluid that issues from the wound is yellowish and contains viral particles that are capable of infecting others. The weeping wounds develop an overlying crust within a day of blister rupture. The scab covers the area for 1 to 2 days.

Patients usually attempt to continue their normal activities during all stages of the infection, with variable degrees of discomfort. For instance, when the scab is in place, it is prone to breaking and bleeding when the lips are stretched during eating, talking, singing, or any other activity involving lip movement. When the original scab is broken, the body next initiates development of a secondary scab.

Following scabbing, the herpes simplex labialis lesion is ready to enter a gradual healing stage. The secondary scabs shrink and slough, followed by the same process in the larger original scab. Healing pink skin replaces the scab, and the area undergoes further healing until it is indistinguishable from the surrounding skin that did not develop lesions. In most cases, there is no residual scarring. The entire process from prodrome to healing is usually no longer than 7 to 10 days, although some patients report a duration of 2 to 3 weeks.3,5

Initial Infecting Event

The majority of people infected with HSV-1 suffered the initial tissue invasion before the age of 10 years.4 The initial event seldom causes any symptoms, although perhaps 15% of victims report the onset of a large mass of blisters 3 to 5 days post event. These blisters involve intraoral tissues and perioral epidermis, and they last for 3 to 5 days. Patients also report malaise, swollen lymph glands, and fever during this time.

Once the virus is present, it cannot be eradicated. It persists for the life of the patient, residing in a state of nonreplicating dormancy in the nerve that supplies the area. For the lips and mouth, this is the trigeminal ganglion.2,5

Triggers of Recurrence

Approximately one-third of persons infected with HSV-1 will experience recurrences.5 A recurrence could possibly be due to a lowering of the immune defenses that would then allow the virus to leave the dormant stage and enter the active infective stage.4 Emotion, injury, and stress are known triggers, and any of them could conceivably compromise host defenses.3-5 Some women report recurrences only during the menstrual cycle or other times of hormonal change.3,4 Another identified trigger is a rise in the body’s core temperature, which occurs with fever (hence the name fever blister) or exposure to the sun, whether occupational or recreational (e.g., tanning). Even being over-heated during the winter has been reported to cause recurrences, as when people dress too warmly.

Transmission and Prevention of Herpes Simplex Labialis

When pharmacists counsel patients with HSV-1 infection, it is helpful to explain how the infection was contracted. An explanation of the transmission process can help patients and their families avoid further spread. Patients must understand that HSV-1 is highly contagious. The greatest point of risk is when blisters appear, as blister exudate contains millions of viral particles. But there is a risk of transferring the virus to others during other stages, and those affected must take great care to guard others from the prodromal stage until full healing is clearly achieved.

Patients with an outbreak must avoid touching the lesions, since virus on the hands can transfer to towels, dishes, or any other item shared with others. They must ensure that others do not drink from a glass they have used. They must completely avoid kissing and oral/genital sexual activity, and they must always ensure that anything that touches their lips is disinfected or immediately discarded, including eating utensils. Sharing lip balms is absolutely prohibited. Parents can transfer the virus to their children during routine child care, as the virus may be on the hands.

Nonprescription Products for HSV-1

The patient who wishes to self-treat HSV-1 has several options.5 The pharmacist can recommend protectants to keep the area moist. These include petrolatum, zinc oxide, allantoin, calamine, and cocoa butter. Some products also contain external analgesics/local anesthetics to decrease the discomfort, such as benzocaine, benzyl alcohol, camphor, dyclonine, menthol, phenol, or pramoxine. Products containing these two groups of ingredients are safe and effective for patients down to the age of 2 years.5 One such product is Blistex Medicated Lip Ointment, which promises to “relieve cold sores.”7 It contains phenol, allantoin, camphor, and menthol. Another is Campho-Phenique Cold Sore Treatment, containing camphor and phenol.8 These interventions provide some palliative relief, but they are unable to reduce the time to healing.9

Docosanol 10% is a radically different nonprescription cold sore therapy, available as the trade-named product Abreva. Docosanol, a fatty alcohol, acts through a mechanism that is unique among all prescription and OTC products currently avail-able: inhibition of viral fusion.2,8,10 This novel mechanism does not lead to emergence of resistant HSV-1.2 Patients are best served by a product that can shorten the duration of discomfort and minimize the disfigurement.11 Research has confirmed that docosanol can achieve these goals; patients who apply it within 12 hours of onset of symptoms will experience a reduced time to healing (as much as 3 days) compared to controls.9,12

Pharmacists should advise patients that Abreva is only to be used in those 12 years of age and older.13 At the first prodromal sign (e.g., tingling), patients should wash their hands and then apply Abreva to the face or lips, rubbing it in gently but completely five times daily until the lesion is healed. Patients should not use docosanol if they are allergic to any of the ingredients. It should be applied only to the affected area, avoiding the eyes and inside of the mouth. Patients should not share the product with anyone else to prevent spread of HSV-1. If the lesion worsens or is not healed in 10 days, the patient should stop using the product and see a physician.

Unproven Products

Several products promoted for cold sores are not proven safe or effective. The list includes dietary supplements (e.g., lysine), lactobacillus probiotics, vitamins, minerals (e.g., zinc), herbals, and homeopathics. Furthermore, patients wishing to purchase Abreva must be cautious, because the manufacturer markets a product under that trade name that does not contain docosanol. Abreva Conceal is a nonmedicated patch that helps hide the cold sore when applied over the area.14,15


What Causes Fever Blisters?

Fever blisters or cold sores are caused by a virus known as herpes simplex virus type 1 (HSV-1). It is similar to the herpes simplex type 2 virus that causes genital herpes. They are so similar that both are capable of infecting the oral or genital tissues.

Recognizing Fever Blisters

Many people know when a fever blister will erupt because they feel a tingling or burning sensation on the area where one has previously appeared—usually the lips or other area surrounding the mouth. This sensation is known as the prodrome. Within a short period, small blisters filled with a clear, yellow fluid appear. The first ones may be sparse, but additional blisters usually continue to appear, creating one large lesion that is disfiguring. During this time, normal oral activities such as talking, singing, and eating are painful. After about 2 days, the blisters begin to break open. The yellowish fluid that leaks from them is highly infectious. Eventually, the blisters begin to heal, and new skin appears.

How Does a Person Get Infected?

A person who is infected with HSV-1 continues to shed the virus. He or she may drink from a cup or straw during an active viral outbreak and transfer the virus to that object. Anyone who uses the cup after this individual can catch the virus. The infected person may also touch the fever blister and get the virus on his or her hands. Anything a patient touches (like doorknobs or school desks) will have active virus that can also be spread to others. Kissing someone during a period of active disease is another way to pass the infection.

Treating Fever Blisters

Some products for fever blisters only provide a certain degree of skin protection and pain relief. They contain such ingredients as protectants (e.g., petrolatum, zinc oxide, allantoin) or anesthetics (e.g., benzocaine, pramoxine, benzyl alcohol). However, such products do not shorten the duration of the lesions. The only nonprescription ingredient that can accomplish this is docosanol, as found in Abreva Cream. Those aged 12 years and above should apply Abreva to the face or lips when they first feel the tingling sensation of the prodrome stage. If applied promptly, docosanol cream can shorten the duration of the outbreak and speed healing. It should be applied five times daily until the fever blisters are fully healed.

Preventing Recurrences

Once you have contracted fever blisters, they cannot be cured. However, you can take some steps to prevent them from coming back. A major trigger of recurrences is body temperature. For some reason, a rise in temperature reactivates the virus. Therefore, you should avoid overexposure to the sun, such as when tanning. Even overwarming yourself by wearing too many layers of clothes in the winter can be enough to cause an outbreak, especially when you are also exercising, as when skiing.


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3. Herpes—oral. MedlinePlus. Accessed March 2, 2015.
4. Fever blisters and canker sores. National Institute of Dental and Craniofacial Research. Accessed March 2, 2015.
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7. Blistex Medicated Ointment. Accessed March 2, 2015.
8. Campho-Phenique Cold Sore Treatment. Accessed March 2, 2015.
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10. Docosanol: new drug. Herpes labialis: barely more effective than an excipient. Prescrire Int. 2009;18(101): 106-107.
11. Sacks SL, Thisted RA, Jones TM, et al. Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: a multicenter, randomized, placebo-controlled trial. J Am Acad Dermatol. 2001;45(2):222-230.
12. Habbema L, De Bulle K, Rooders GA, Katz DH. n-Docosanol 10% cream in the treatment of recurrent herpes labialis: a randomized, double-blind, placebo-controlled study. Acta Derm Venereol. 1996;76(6):479-481.
13. Abreva. Amazon. Accessed March 2, 2015.
14. Abreva Cream FAQs. GlaxoSmithKline. Accessed March 2, 2015.
15. Abreva Conceal hides your cold sore. GlaxoSmithKline. Accessed March 2, 2015.
16. Carmex. Accessed March 2, 2015.

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