Cold sore management in the community

Cold sores & causes

A cold sore is a mild, self-limiting infection of the lips, cheeks or nose caused by the oral herpes simplex virus. HSV-1 type 1 is implicated in more than 90% of cases of cold sores. A cold sore infection is very common, 20-50% of people will experience it at some point in their lifetime. Individuals with recurrent cold sores will have 2-3 episodes a year, and in some cases up to 6 times a year (Rutter, 2017).

Cold sores are a result of an infection by HSV type 1. The virus is acquired at mucosal surfaces or through breaks in the skin, it then spreads to the epidermis and multiplies. The virus lies dormant in the trigeminal nerve until reactivation by a trigger. Reactivation leads to either asymptomatic shedding of the virus or symptoms such as tingling, burning then eventual lesions (BMJ, 2021). Common triggers include:

• UV light - sunlight
• Stress
• A viral infection such as a cold
• A weakened immune system

Clinical features:

Cold sores typically present in two stages:

1. Prodromal stage: Comprises of symptoms such as tingling, itching or burning around the mouth or other areas of the face.
2. Approximately 24 hours after the prodromal stage, lesions start to appear as blister or vesicles which quickly grow. They are painful, itchy, and usually weep and crust over within a day (Rutter, 2017).

Red flags associated with cold sores require referal to a doctor and consist of the following:

• Symptoms which last more than 14 days.
• Lesions inside the mouth.
• Widespread and severe lesions.
• Lesions that spread from the lips to other areas of the face.
• Immunocompromised patients or those taking immunosuppresive medication.

Differential diagnosis (questions to ask the patient):

The following questions provide a non-exhaustive list of questions that should be asked to patients which present with suspected cold sores.

1. Did you experience any warning symptoms such as tingling or a burning sensation around the lips? 
   • Yes: Likely a cold sore, ask further questions
   • No: Refer for further investigation, cold sores typically present with prodromal features - patients without these symptoms are likely to suffer from other conditions such as impetigo or angular chelitis.
2. Are the cold sores localised around the mouth?
   • Yes: Likely a cold sore, ask further questions
   • No: If inside the mouth or spread out around the face refer for further investigation. Impetigo or aphthous ulcers may be the causes in these instances.
3. Have you had the symptoms for more than 14 days?
   • Yes = Refer for further investigation, as cold sores are self-limiting and should have been resolved within 14 days.
   • No = Ask further question
4. Any known trigger factors such as stress, sunlight or a viral infection?
   
   • Yes = Likely a cold sore, provide advice and treatment for this
   • No = Lesions without any triggers should be referred to rule out any sinister pathology.

Treatments:

Aciclovir 5% w/w cream (General Sale List)

• Mechanism: Acyclovir is converted to aciclovir triphosphate through a series of reactions. It has a high affinity for DNA polymerase, allowing it to be incorporated into the DNA of the virus causing chain termination. It also competes for viral polymerase, preventing other bases from binding to it and inactivates it (DrugBank, 2021).
• Indication: For treatment of herpes simplex infections of the face and lips.
• Side-effects: Itching, headache, drying of the skin or mild flaking (components of the cream can cause contact dermatitis).
• Counselling:
  • Start treatment at the onset of prodromal symptoms or signs.
  • Cautious use during pregnancy or breastfeeding as oral form has been detected in breast milk (NICE, 2016).
• Evidence: A double-blind randomised, patient-initiated trial, aciclovir was shown to be effective in treating lesions associated with cold sores. Patients had a quicker resolution of symptoms when they started treatment in prodromal phase. Frequency of lesions was also significantly lower in the aciclovir treatment group in comparison to placebo group (Spruance, 1990).

Penciclovir 1% w/w cream (General Sales List)

• Mechanism: Penciclovir is converted to penciclovir triphosphate through a series of reactions. It competes with deoxygenase triphosphate, inhibiting viral replication of virus-infected cells by inhibiting DNA synthesis (DrugBank, 2021).
• Indication: Treatment of herpes simplex virus infections of the lips and face (emc, 2021).
• Side-effects: Administration site conditions such as burning sensation or pain, contact dermatitis.
• Counselling:
  • Start treatment at the onset of prodromal symptoms.
• Evidence: Penciclovir cream demonstrated efficacy in the treatment of herpes simplex labialis. In a RCT, topical penciclovir provided faster healing and pain resolution in comparison to a placebo. It was effective in both the prodrome and lesion stages (Spruance S. L., 1997).

Docosanol 10% w/w cream (General Sales List)

• Mechanism: Prevents the entry of the HSV into the cells and its viral replication. It inhibits the fusion between the human cell membrane and the viral envelope. (DrugBank, 2021)
• Indication: Healing cream for treatment of cold sores and fever blisters.
• Side-effects/Cautions: Redness or swelling may occur, stop use and inform your doctor or pharmacist as soon as possible. Seek urgent medical care if you have any symptoms of an allergic reaction such as a rash.
• Evidence: In a double-blind placebo-controlled trial, Docosanol showed reduced times for symptoms of cold sores. Healing time was significantly faster than placebo, with only mild adverse effects (Sacks, 2001).

Paracetamol 500 mg tablets (General Sales List)

• Mechanism: Reduces the synthesis of prostaglandins by inhibiting the COX pathway, this provides pain relief.
• Indication: Analgesia, reduces pain associated with cold sores.
• Side-effects: Side effects from paracetamol are rare but can include (NHS Inform, 2021); an allergic reaction (rash and swelling) liver damage and kidney damage.
• Counselling:
  • Do not take any other products containing paracetamol at the same time.
  • Do not take more than 8 tablets in 24 hours.
  • Visit the A & E as soon as possible if you take more than the recommended maximum dose.
• Evidence: Multiple studies over time support the use of paracetamol in acute pain management. It has been shown to be better than placebo in providing pain relief, as a result it can be used in reducing pain associated with cold sores.

Lysine tablets or lip balm (General Sales List)

• Mechanism: L-lysine in high concentrations can inhibit viral replication and cytopathogenicity of the HSV (DrugBank, 2021).
• Indication: Helps the healing of cold sores and reduces the chances of getting cold sores.
• Side-effects/caution: It can cause side-effects such as diarrhoea and stomach pain.
• Counselling:
  • Do not share lip balm with others
• Evidence: In double-blind multicenter study of lysine for the treatment of HSV, lysine was shown to be effective in reducing the occurrence, severity, and healing time for HSV infections (Griffith, 1987).

Self care advice for patients:

• Lesions should heal without scarring.
• Avoid trigger factors if possible. If sunlight is a trigger factor, use sunscreen or sunblock to reduce recurrence.
• Avoid touching lesions, kissing, oral sex or sharing items such as lipstick to reduce transmission.
• Wash hands with soap and water after applying topical preparations.
• Take care when using contact lenses, to prevent transmission to the eyes.
• Seek medical advice if symptoms worsen or there is no improvement seen up to 7 days after initiating treatment.

References:

BMJ. (2021). Herpes simplex virus infection. Retrieved from BMJ Best Practice: https://bestpractice.bmj.com/topics/en-gb/53/aetiology

DrugBank. (2021). Acyclovir: Uses, Interactions, Mechanism of Action | DrugBank Online. Retrieved from DrugBank Online: https://go.drugbank.com/drugs/DB00787

DrugBank. (2021). Docosanol: Uses, Interactions, Mechanism of Action | DrugBank Online. Retrieved from DrugBank Online: https://go.drugbank.com/drugs/DB00632

DrugBank. (2021). Lysine: Uses, Interactions, Mechanism of Action | DrugBank Online. Retrieved from DrugBank Online: https://go.drugbank.com/drugs/DB00123

DrugBank. (2021). Penciclovir: Uses, Interactions, Mechanism of Action | DrugBank Online. Retrieved from DrugBank Online: https://go.drugbank.com/drugs/DB00299

DrugBank. (2021). Valaciclovir: Uses, Interactions, Mechanism of Action | DrugBank Online. Retrieved from DrugBank Online: https://go.drugbank.com/drugs/DB00577

Drugs.com. (2021). Topical astringents. Retrieved from Drugs.com: https://www.drugs.com/drug-class/topical-astringents.html

emc. (2021). Fenistil Cold Sore Cream - Summary of Product Characteristics (SmPC) - (emc). Retrieved from emc : https://www.medicines.org.uk/emc/medicine/21081/SPC/FenistilColdSoreCream

Griffith, R. S. (1987). Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica, 183-190.

NHS Inform. (2021). Paracetamol. Retrieved from NHS Inform: https://www.nhsinform.scot/tests-and-treatments/medicines-and-medical-aids/types-of-medicine/paracetamol

NICE. (2016, 10). Herpes Simplex - oral: Oral antiviral drugs. Retrieved from NICE CKS : https://cks.nice.org.uk/topics/herpes-simplex-oral/prescribing-information/oral-antiviral-drugs/

NICE. (2021). VALACICLOVIR | Drug | BNF content published by NICE. Retrieved from BNF NICE: https://bnf.nice.org.uk/drug/valaciclovir.html

Rutter, P. (2017). Cold Sores (Herpes simplex Labilis). In P. Rutter, Community Pharmacy; Symptoms, Diagnosis and Treatment (pp. 259-262). Elsevier.

Sacks, S. L. (2001). Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial. Journal of the American Academy of Dermatology, 22-230.

Spruance, S. L. (1990). Treatment of recurrent herpes simplex labialis with oral acyclovir. The Journal of infectious diseases, 185-190.

Spruance, S. L. (1997). Penciclovir cream for the treatment of herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group. JAMA, 1374-1379.

Spruance, S. L.-C. (2003). High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of two randomized, placebo-controlled, multicenter studies. Antimicrobial agents and chemotherapy, 1072-1080.