- The development of cold sores is related to 2 herpes simplex viruses: herpes
simplex-1(HSV-1) and herpes simplex-2 (HSV-2).
- HSV-1, which is most commonly transmitted via saliva, causes the majority of oral herpes infections.
- HSV-2, which is present in genital secretions, causes the majority of genital herpes infections, but may also present orally as a result of orogenital transmission.
- Cold sores are a common problem affecting up to 80% of adolescents & adults, and approximately 33% of school age children.
- About 20 to 40% of patients who experience a primary herpes infection develop subsequent recurrent herpes infections caused by reactivation of HSV that remains latent in neural ganglion cells.
- sun exposure
- physical or surgical trauma
- dental extractions
- menses and other hormonal changes
- infectious febrile conditions
- upper respiratory tract infection
- Risk factors:
- female sex
- older age (>65)
- weakened immune system
- For more information and photos, go to:
- DermNet NZ
- Typically presents as a unilateral vesicular lesion surrounded by erythema, appearing on the vermilion border of the lip.
- The vesicles break, leaking a clear, sticky fluid, then crust over and heal without scarring within 7 to 10 days.
- Prodromal itching, tingling or burning sensations in the location of the eruption may occur 2 to 24 hours before the appearance of the vesicle, but this does not occur in all cases.
- Patients complain of discomfort and unsightly appearance.
- Although some stages (e.g., prodrome, early blister stage prior to rupture, blisters post-crust formation) may pose slightly less risk than others, the possibility of transmission is virtually always present.
- Systemic symptoms (e.g fever) are unusual and should cause suspicion for another condition.
Herpes labialis (cold sore) is diagnosed based on the presence of typical signs and symptoms. Rule out the following conditions that may present with similar signs/symptoms:
- Impetigo - a bacterial infection most commonly caused by staphylococcus aureus. Can cause pustules to form around the mouth. It will be non-inflamed and the lesions will have honey-coloured crusts, in contrast to the clear crusts seen with cold sores.
- Canker sores - lesions that occur on the inside of lips and are not preceded by formation of a vesicle. Will not occur on external lip.
- Angular cheilitis - inflammation that occurs on the corners of the mouth, which can resemble a cold sore. However, angular cheilitis will not cause any lesions to form.
- Chicken pox - presence of typical lesions on skin and mucous membranes, spread to head, trunk and extremities. Lesions can occur rarely on the mucocutaneous border of the lip, which resemble cold sore lesions, but lesions will be present elsewhere as well.
- Shingles (Herpes zoster) - clinical diagnosis is based on vesicular eruption on one side only, often with prodromal pain which may involve sensory nerves and overlying skin of head, trunk or limbs. Lesions on or around nose may involve the eye (herpes keratitis) and require immediate assessment by patient's primary care provider.
- Mononucleosis which usually involves close contact with other infected persons and includes generalized swollen lymph nodes, especially in the neck and groin. Fever is also possible. Blisters may occur on the lips which resemble a cold sore lesion. Refer to patient's primary care provider for blood tests and diagnosis.
- Basal cell carcinoma - non-healing lesions which may resemble cold sores on face. Suspect this if the lesion has not healed or changed over 10 days.
- Stevens-Johnson syndrome - a fever-causing, skin-peeling reaction in response to a drug.
- Syphilis - a painless sore on the lips or in the mouth occurring 10 days to 3 months after contact with an infected person. Since they are painless and not itchy, this helps differentiate them from a cold sore. Refer to patient's primary care provider for diagnosis and antibiotic treatment.
Patients with typical cold sore signs/symptoms usually do not require further investigation, however, an assessment by the patient's primary care provider may be required in the following situations.
- First cold sore and accompanied by fever, malaise, pharyngitis or stomatitis
- May be primary infection of herpes labialis; longer duration of anti-viral treatment may be indicated.
- Patient age <12 years old
- Patient is immunocompromised (drug or disease)
- Lesion present for greater than 14 days
- Lesion appears infected - excessively red, swollen, or contains pus
- Lesion on or around the nose, or if there is ocular involvement
- Accompanied by symptoms of systemic illness (fever, swollen glands)
- Frequent recurrences (>6 per year), since chronic prophylactic therapy may be more appropriate. Note: you may still prescribe for the current episode.
- Unable to confirm patient's diagnosis of cold sore and more serious condition (see Differential Assessment above) is suspected. Refer to patient's primary care provider for further investigation and supervised therapy.
Goals of therapy include decreasing discomfort, viral shedding & duration/severity , as well as preventing secondary bacterial infection & recurrences.
- Patients should keep the area clean using mild soap and water and avoid touching the lesion to prevent autoinoculation and spread of HSV.
- Avoid kissing or oral sex until all lesions are completely healed.
- Do not share personal items in contact with lesions (e.g. lip balm, towels, cosmetics, eating utensils).
- Ensure proper hand hygiene is followed to reduce the risk of transferring the infection to other parts of the body. (e.g. eye)
- Cold or warm compresses can help clean the area and improve the appearance of the lesions.
Over-the-counter drug options
- Pharmacists can recommend protectants such as petrolatum, zinc oxide, cocoa butter, allantoin or calamine to prevent cracking and drying. If a secondary bacterial infection occurs, refer to patient's primary care provider.
- Local anesthetics can offer temporary relief from pain and itching. Examples are Zilactin B® or Anbesol® which contain benzocaine.
- Docosonal 10% is in Abreva® and appears to block viral entry by inhibiting fusion between lipid-enveloped viruses and plasma membrane of the host cell, which means it prevents the virus from spreading to healthy cells. Apply 5x/day at first symptoms.
- Lipactin® contains zinc and heparin. It may reduce pain and increase rate of healing of the lesion, although there are no studies to support this.
- Sunscreens are useful adjuncts in preventing sun-induced recurrences. Suggest SPF 30 or higher applied 30 minutes prior to exposure.
Prescription drug options
- Can be prescribed for treatment of recurrent herpes labialis occurring in immunocompetent adults (level 1 evidence).
- Treatment should be started as soon as possible, ideally within 1-2 hours after onset of first symptoms ( prodromal itching, tingling or burning). Oral antivirals are ineffective if started after the lesion appears.
- Reduces the duration of symptoms by an average of one to two days, reduces pain and itch, and improves appearance. Will not abort a lesion entirely.
- Many patients have only occasional recurrences of cold sores with minimal symptoms; antiviral therapy is not necessary for these patients.
- Only consider prescription treatment if the patient has a well-defined prodrome and lesion has not yet formed. If a lesion has formed, patients may be issued a prescription to keep on hand to facilitate early initiation of therapy for future episodes.
- Oral antivirals indicated for cold sore treatment:
- ACYCLOVIR: 400mg 5 times per day for 5 days
- VALACYCLOVIR: 2000 mg BID for 2 doses (every 12 hours)
- FAMCICLOVIR: 750mg BID for 2 doses (every 12 hours) or one dose of 1500 mg
- Suppressive therapy with acyclovir may also be prescribed if there is a known trigger for the patient's cold sores (eg. sun exposure).
- ACYCLOVIR: 400mg BID beginning 12h prior to trigger exposure & for duration of exposure
- Renal dosing:
|Drug||Renal Dose Adjustment|
CrCl <20 mL/minute: Administer 250 mg as a single dose
CrCl 20-39 mL/minute: Administer 500 mg as a single dose
CrCl 40-59 mL/minute: Administer 750 mg as a single dose
CrCl ≥60 mL/minute: No dosage adjustment necessary
CrCl 10-29 mL/minute: 500 mg every 12 hours for 2 doses
CrCl 30-49 mL/minute: 1 g every 12 hours for 2 doses
Dosing has not been established for this indication
- Pregnancy: acyclovir and valacyclovir can be used during pregnancy; insufficient data available to evaluate famciclovir safety.
- Lactation: acyclovir and valacyclovir are rated as compatible with breastfeeding; insufficient data available on the safety of famciclovir.
- Acyclovir 5% / hydrocortisone 1% cream (Xerese®) is now available to prescribe
- Must be started within prodromal phase, as with oral antivirals.
- Applied five times daily for 5 days.
- Topical antivirals are slightly less effective versus oral antivirals. Topical antivirals will reduce lesion duration by about 1/2 day, versus one to two days with oral antivirals.
- Better tolerated by some patients.
- Require frequent application & carry risk of self inoculation.
Advice on minimizing the spread of the infection
- Try to avoid touching your cold sores, unless you are applying a cream. Creams should
be dabbed on gently rather than rubbed in, as this can damage your skin further.
- Always wash your hands before, and after, applying cream, and after touching the affected area.
- Do not share creams with others because this can cause the infection to spread.
- Do not share items that come into contact with the affected area, such as lipsticks, or cutlery.
- Avoid kissing or oral sex, until your cold sores have completely healed.
- If you have a cold sore, be particularly careful around newborn babies, pregnant women, and people with a low immune system such as those who have been undergoing chemotherapy, or those with HIV.
Preventing recurrent outbreaks of cold sores
- If you know what usually triggers your cold sores, try to avoid these triggers if possible. For example, a sun block lip balm (SPF 30 or higher) applied 30 minutes prior to exposure may help to prevent cold sores triggered by sunlight.
- There is no benefit in using an antiviral cream continuously to try and prevent future bouts of cold sores. They cannot cure the virus, and will only be effective once the virus has been triggered.
- For individuals in whom orolabial herpes is reactivated by exposure to sunlight, oral acyclovir 400 mg BID begun 12 hours prior to sun exposure, with frequent sunscreen use, prevents attacks. Prophylaxis is continued for the duration of sun exposure.
- Follow-up with patient after 7 days.
- If symptoms are not resolved, refer to patient's primary care provider.
- If symptoms are resolved, advise on prevention strategies above.
- Patients who have frequent episodes of cold sore may be given a prescription for an antiviral to keep on hand for future episodes.
Assess Adverse Effects
- Oral antivirals are well tolerated; frequency of adverse effects similar to placebo. Some patients may experience a mild headache.
Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in the CPS (e-CPS), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca). This information should be routinely consulted before prescribing.
|500mg tablet & 1000mg tablet*|
|125mg tablet*, 250mg tablet* & 500mg tablet|
|200mg tablet & 400mg tablet|
|Acyclovir 5% / Hydrocortisone 1% cream* (Xerese®)|
|Note: topical acyclovir 5% cream and ointment (Zovirax®) is not approved for cold sore treatment by Health Canada, & therefore, cannot be prescribed by a pharmacist.|
*Not a listed benefit of the Saskatchewan Drug Plan. Pharmacists may prescribe & assessment fee may be claimed.
- pseudoDIN: 00951088
- Max of 8 claims per 365 days per patient
- Max of 8 claims per 365 days per patient
- May prescribe sufficient quantity to treat ONE cold sore. No refills.
- If patient presents with a cold-sore beyond the pro-dromal stage, you may still prescribe enough tablets to treat the next episode.
- Each cold sore is to be treated as a distinct episode and re-assessed.
- If exposure to a known trigger is expected, you may prescribe suppressive therapy with acyclovir.
- Once the pharmacist completes the 7 day follow up, patients who have frequent episodes of cold sore may be given a prescription for an antiviral to keep on hand for future episodes.
- Note: topical acyclovir 5% cream and ointment (Zovirax®) is not approved for cold sore treatment by Health Canada, & therefore, cannot be prescribed by a pharmacist.
- Only products with an official indication for cold sores from Health Canada are approved for pharmacist prescribing. Only the active ingredients in the "products" section are approved for pharmacist prescribing.
Evans G. Herpesvirus infections. In RxTx - CTC online. Available at www.e-therapeutics.ca (by subscription).
Conklin J. Cold sores (Herpes labialis). In RxTx - CTMA. Available at www.e-therapeutics.ca (by subscription).
Pray WS. Preventing and Treating Cold Sores. In Medscape. Free access at http://www.medscape.com/viewarticle/557162.
Opstelten W, Neven A, Eekhof J. Treatment and prevention herpes labialis Canadian Family Physician 2008;54:1683-7. Available at http://www.cfp.ca/content/54/12/1683.full ( free access).
Klein, Robyn. Treatment of herpes simplex virus type 1 infection in immunocompetent patients. In UpToDate online. Available at www.uptodate.com (by subscription).
Oral herpes. In Dynamed online. Available at www.dynamed.com (by subscription).
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Reviewed by Dr. Yvonne Shevchuk, College of Pharmacy & Nutrition.