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Infections and infestations Oral health

Herpes simplex - oral

Last revised in May 2024

Oral herpes simplex virus (HSV) usually causes a mild, self-limiting infection of the lips, cheeks, nose or oropharynx

Herpes simplex - oral: Summary

  • Oral herpes simplex virus (HSV) usually causes a mild, self-limiting infection of the lips, cheeks, or nose (herpes labialis or 'cold sores') or oropharyngeal mucosa (gingivostomatitis).
    • Herpes simplex virus type 1 (HSV-1) is the cause in more than 90% of cases. Rarely, infections may be caused by HSV type 2 (HSV-2).
    • Most HSV-1 infections are subclinical and asymptomatic.
    • Symptomatic primary infection usually presents as gingivostomatitis in children.
  • HSV-1 is usually transmitted via direct contact with infected secretions entering via the skin or mucous membranes, from a person who is actively shedding the virus.
  • Oral HSV infection can cause severe or life-threatening complications, particularly in immunocompromised people, including eczema herpeticum, eye disease including corneal ulceration, erythema multiforme, pneumonia, and encephalitis.
  • Primary herpes labialis lesions usually resolve within 10–14 days; gingivostomatitis usually resolves within 2–3 weeks.
  • The diagnosis of oral herpes simplex infection is based on the person's age and clinical features, such as the history, location, and appearance of lesions.
    • Herpes labialis may present with a prodrome of fever, sore throat, and lymphadenopathy, particularly in primary infections.
    • Initial symptoms of pain, burning, tingling, and itching may precede visible lesions and typically last 6–48 hours.
    • Herpes labialis lesions are typically crops of vesicles that rupture, ulcer, crust, and heal (usually without scarring).
    • Herpes gingivostomatitis lesions are typically crops of painful vesicles that rupture and form ulcers on the pharyngeal and oral mucosa.
    • People who are immunocompromised may have severe, atypical lesions anywhere in the oral cavity.
  • Assessment of a person with suspected oral herpes simplex infection should include:
    • Any known trigger factors, such as ultraviolet light, stress, fever, or trauma to the area.
    • Any red flags for oral cancer.
  • Investigations are not usually needed in primary care.
  • Management of a person with suspected oral herpes simplex should include:
    • Arranging hospital admission if the person is unable to swallow or is dehydrated; is immunocompromised with severe infection; or a serious complication is suspected.
    • Seeking specialist advice or referral if the person is immunocompromised with troublesome infection; is pregnant; has frequent, persistent, or severe infections; has associated recurrent erythema multiforme; lesions are refractory to primary care treatment; or lesions are atypical. 
  • Management of oral herpes simplex infection includes:
    • Offering analgesia to treat pain and fever, if needed.
    • Considering prescribing an oral antiviral such as aciclovir or valaciclovir, for healthy people with a primary infection or recurrent infection with frequent, persistent, or severe lesions; people with recurrent gingivostomatitis; and people who are immunocompromised with primary or recurrent infection, depending on clinical judgement.
    • Advising that topical antiviral preparations, topical analgesics, mouthwash, and lip barrier preparations are not routinely recommended, but some people may find them helpful, and they are available over-the-counter.
    • Offering self-care advice to avoid trigger factors, if possible, and to reduce the risk of autoinoculation and transmission to other people.
    • The use of sunscreen or sunblock lip balm for people with recurrent infections triggered by sunlight.

Have I got the right topic?

From age 6 months onwards.

This CKS topic covers the management of oral herpes simplex including oral herpes labialis (cold sores) and gingivostomatitis.

This CKS topic does not cover herpetic whitlow, eczema herpeticum, or other herpes infections such as herpes zoster virus.

There are separate CKS topics on Aphthous ulcer, Chickenpox, Herpes simplex - genital, Herpes simplex - ocular, Palliative care - oral, and Shingles.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

May 2024 — minor update. The dosage regimen for aciclovir has been aligned to the manufacturer's summary of product characteristics. 

Previous changes

January 2023 — minor update. Tubulointerstitial nephritis added as a potential adverse effect of valaciclovir in line with an update to the manufacturer's summary of product characteristics. 

September to October 2021 — reviewed. A literature search was conducted in September 2021 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes to the recommendations have been made.

September to October 2016 — reviewed. A literature search was conducted in September 2016 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials since the last revision of this topic. The recommendations on primary care management and referral have been updated in line with current evidence. The topic has also undergone minor restructuring.

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

August 2012 — reviewed. A literature search was conducted in August 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. No major changes to clinical recommendations have been made.

July 2011 — minor update. More exact paracetamol dosing for children has been introduced by the Medicines and Healthcare products Regulatory Agency (MHRA) document Press release: more exact paracetamol dosing for children to be introduced (2011). Prescriptions have been updated to reflect the revised dosing. 

March 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

May 2009 — minor update. Topical products containing choline salicylate (such as Bonjela®) are no longer licensed for use in children under 16 years of age because of the theoretical risk of Reye's syndrome if they are overused. The prescriptions have been updated accordingly. 

April 2008 — minor update to text following late comments from an external reviewer.

September to December 2007 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

October 2006 — minor update. Analgesia prescriptions updated because new doses of ibuprofen for children are recommend by the British National Formulary. 

November 2005 — minor technical update. 

July 2005 — updated to incorporate the document Referral guidelines for suspected cancer (2005) published by the National Institute for Health and Clinical Excellence (NICE). 

June 2004 — reviewed. Validated in September 2004 and issued in November 2004.

January 2002 — rewritten. Validated in March 2002 and issued in April 2002.

August 1998 — written, replacing guidance called Herpes simplex gingivostomatitis.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 October 2021.

HTAs (Health Technology Assessments)

No new HTAs since 1 October 2021.

Economic appraisals

No new economic appraisals relevant to England since 1 October 2021.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 October 2021.

Primary evidence

No new randomized controlled trials in the major journals since 1 October 2021.

New policies

No new national policies or guidelines since 1 October 2021.

New safety alerts

No new safety alerts since 1 October 2021.

Changes in product availability

No changes in product availability since 1 October 2021.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

  • Diagnose herpes labialis and gingivostomatitis.
  • Offer appropriate symptom relief and drug treatment.
  • Provide advice to reduce the risk of transmission and autoinoculation of herpes simplex virus, and to reduce the risk of complications.
  • Seek specialist advice, or refer when appropriate.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

  • Non-steroidal anti-inflammatory drugs (NSAIDs)
    • Review the appropriateness of non-steroidal anti-inflammatory drug (NSAID) prescribing widely and on a routine basis, especially in people who are at higher risk of gastrointestinal, renal and cardiovascular morbidity and mortality (for example, older people).
    • If an NSAID is needed, use ibuprofen (1,200 mg a day or less) or naproxen (1,000 mg a day or less). Use the lowest effective dose and the shortest duration of treatment necessary to control symptoms.
    • Co-prescribe a proton pump inhibitor with NSAIDs for people who have osteoarthritis or rheumatoid arthritis, and think about the use of gastroprotective treatment when prescribing NSAIDs for low back pain, axial spondyloarthritis, psoriatic arthritis and other peripheral spondyloarthritides.

[NICE, 2018]

NICE quality standards

No NICE quality standards were found during the review of this topic.

Background information

What is oral herpes simplex?

  • Oral herpes simplex virus (HSV) usually causes a mild, self-limiting infection of the lips, cheeks, or nose (herpes labialis or 'cold sores') or oropharyngeal mucosa (gingivostomatitis) [Worrall, 2009; Usatine, 2010a].
  • Primary infection refers to first-time exposure to HSV-1 or HSV-2 in a previously HSV seronegative person [Sawleshwarkar and Dwyer, 2015], and typically occurs in children under 5 years of age in the case of HSV-1 [Goldman, 2016; PCDS, 2021].
    • Most HSV-1 infections are subclinical and asymptomatic, and therefore do not present to a healthcare professional [PCDS, 2021].
    • Symptomatic primary infection usually presents as gingivostomatitis in children, and is often associated with a pharyngitis in young adults [PCDS, 2021].
    • Following a primary infection, HSV-1 migrates to the local sensory ganglia (typically the trigeminal nerve ganglion), where it can remain latent indefinitely, or reactivate to cause clinical infection or asymptomatic viral shedding [Williams, 2011; Stoopler and Sollecito, 2014].
  • Recurrent infection refers to clinically evident herpes simplex lesions in a person with usually previous HSV-1 infection — recurrent infections are more frequent in the 6 months following a primary infection [Sawleshwarkar and Dwyer, 2015].
    • About 90% of recurrent HSV-1 infections cause herpes labialis. Recurrent gingivostomatitis is more rare, and usually occurs in people who are immunocompromised [Usatine, 2010a].

How is herpes simplex transmitted?

  • Herpes simplex virus type 1 (HSV-1) is usually transmitted during childhood via direct contact with infected secretions entering via the skin or mucous membranes, from a person who is actively shedding the virus to a HSV-seronegative person [Esmann, 2001; Torres, 2007; PCDS, 2021].
    • The virus can be transmitted by salivary transfer by kissing or sharing utensils or towels, if there is contact with mucus membranes or open or abraded skin [Usatine, 2010a].
    • A person sheds HSV-1 for a median duration of 4–60 hours after the onset of symptoms [Torres, 2007], and HSV can be transmitted from oral mucosa or skin surfaces that appear normal when no clinical lesions are present [Stoopler, 2012; BMJ Best Practice, 2021].
    • Lesions are most contagious at the time of vesicular rupture, and continue to be contagious until they have scabbed [AAOM, 2016].
  • Primary infection appears 2–26 days after contact with an infected person [Usatine, 2010a; George, 2014].
  • HSV persists in a latent state in sensory dorsal root ganglia proximal to the site of infection (typically the trigeminal nerve ganglion), where it can remain latent indefinitely, or reactivate to cause clinical infection or asymptomatic viral shedding [Williams, 2011; Stoopler and Sollecito, 2014; BMJ Best Practice, 2021; PCDS, 2021].

How common is oral herpes simplex?

  • Data from 2016 suggests that the global prevalence of HSV-1 infection at any site in people aged 0–49 years is 67% [James, 2020].
  • Studies from the US have found that by the age of 5 years, seroprevalence of HSV is 20% and that around one third of children aged 6–13 years have acquired HSV-1 infection [Ahluwalia, 2019].
  • It has been estimated that about 40% of people who have had a primary infection will have recurrent oral herpes simplex infections [George, 2014].
  • Recurrences typically occur 2–3 times a year [Bentley, 2003], but may occur up to 6 times a year [Kolokotronis, 2006; Cernik et al, 2008].
    • Recurrent herpes labialis is more commonly seen in healthy people. Typically, the number of recurrent episodes decreases after the age of 35 years [Opstelten, 2008].
    • In contrast, recurrent gingivostomatitis is more commonly seen in people who are immunocompromised [Stoopler, 2012].

What are the complications of oral herpes simplex?

  • In most people, oral herpes simplex virus (HSV) infection is a mild, self-limiting illness, but it can cause severe or life-threatening complications, particularly in immunocompromised people. Possible complications include:
    • Dehydration — from poor oral intake due to painful swallowing, and fever (especially in young children with primary herpes gingivostomatitis).
    • Herpetic whitlow (from autoinoculation) — vesicular lesions on the hands or digits, for example in thumb-sucking children. For more information, see the CKS topic on Whitlow (staphylococcal and herpetic).
    • Eczema herpeticum — extensive eruptions of herpes simplex in people with atopic eczema, often affecting the face and neck. For more information, see the CKS topic on Eczema - atopic.
    • Labial (lip) adhesions — a rare complication of herpes gingivostomatitis which causes labial epithelization due to adherent ulcer healing, which may limit mouth opening.
    • Eye disease (including herpetic keratoconjunctivitis, corneal ulceration, and acute retinal necrosis) from autoinoculation. For more information, see the CKS topic on Herpes simplex - ocular.
    • Herpes gladiatorum — vesicular eruptions on the torso, or anywhere that has had skin-to-skin contact, typically seen in people who play contact sports such as rugby and wrestling.
    • Herpes sycosis of the beard area — a follicular infection with HSV-1 which causes vesicopapular lesions in the beard area, often caused by autoinoculation from shaving.
    • Erythema multiforme — a hypersensitivity reaction often triggered by recurrent HSV that typically produces target-shaped lesions, often on distal extremities.
    • Tracheobronchitis, pneumonia, and oesophagitis (from direct extension of oropharyngeal infection).
    • Aseptic meningitis, encephalitis, myelitis, and radiculopathy (rare).
    • Hepatitis (rare).

[Thomas, 2007; Worrall, 2009; Usatine, 2010a; Williams, 2011; Stoopler and Sollecito, 2014; Sawleshwarkar and Dwyer, 2015; Goldman, 2016]

What is the prognosis of oral herpes simplex?

Diagnosis

When should I suspect oral herpes simplex?

The diagnosis of oral herpes simplex is based on the person's clinical features, such as the history, location, and appearance of lesions. Be aware that a person may have prodromal symptoms without developing typical herpes lesions.

  • Suspect herpes simplex labialis (cold sores) if a person presents with:
    • A prodrome of pain, burning, tingling, itching, and paraesthesia which precedes the lesions and typically lasts 6–48 hours.
    • Crops of vesicles that rupture, leaving superficial ulcers that crust over and heal (usually without scarring), typically at the mucocutaneous junction of the lips (most commonly the lower lip). Infections may occur at the same site for each recurrent episode.
  • Suspect herpes gingivostomatitis if a person presents with:
    • A prodrome of fever, general malaise, sore throat, and cervical and submandibular lymphadenopathy, particularly in primary (rather than recurrent) infections.
    • A sore mouth or throat, with excess salivation and drooling (particularly in children).
    • Crops of painful vesicles on a red swollen base that often rupture and form ulcers on the pharyngeal and oral mucosa (palate, buccal mucosa, tongue, gingiva, and floor of the mouth). Areas of ulceration may be covered by yellow/grey membranes.
  • Be aware that in people who are immunocompromised, oral herpes infection can be severe, with atypical single or multiple necrotizing lesions anywhere in the oral cavity, which may be large and persistent.

Basis for recommendation

The information on when to suspect oral herpes simplex infections is based on expert opinion in international review articles [Usatine, 2010b; Williams, 2011; Stoopler, 2012; George, 2014; Stoopler and Sollecito, 2014; BMJ Best Practice, 2021].

  • Prodromal symptoms of pain, burning, tingling, itching, and paraesthesia typically precede clinical lesions in about 60% of people with recurrent infections [Usatine, 2010a].
  • The information that people who are immunocompromised may have more severe episodes of primary infection or more severe reactivation of herpes simplex virus infection is based on expert opinion in a review article published by the British HIV Association (BHIVA) [Williams, 2011].

How should I assess a person with oral herpes simplex?

In a person presenting with suspected oral herpes simplex:

  • Ask about:
    • The location of lesions.
    • The frequency and duration of lesions.
    • Associated symptoms, such as pain.
    • Known trigger factors, such as exposure to prolonged bright ultraviolet light, physical or emotional stress, fatigue, fever, menstruation, immunosuppression, extremes in temperature, mouth or lip trauma to the area of primary infection, and dental or surgical procedures.
    • Any associated complications.
    • Any underlying medical conditions that may affect the course of herpes simplex infection, such as immunosuppression or atopic eczema.
  • Assess for any red flags that may suggest more serious underlying disease such as oral cancer, including:
    • Unexplained ulceration in the oral cavity lasting for more than 3 weeks.
    • A suspicious lump on the lip or in the oral cavity.
    • A red, or red and white, patch in the oral cavity consistent with erythroplakia or erythroleukoplakia.
    • For more information, see the CKS topic on Head and neck cancers - recognition and referral.
  • Investigations are not usually necessary in primary care.
    • If a person presents with unexplained recurrent infections which are severe or persistent, consider arranging investigations for underlying immunosuppression, such as HIV infection, depending on clinical judgement. For more information, see the CKS topic on HIV infection and AIDS.

Basis for recommendation

Initial assessment

The recommendations on how to assess a person with suspected oral herpes simplex are largely based on expert opinion regarding the typical characteristics of, and risk factors for infection detailed in a British Medical Journal (BMJ) Clinical Evidence review article Herpes labialis [Worrall, 2009], a Cochrane systematic review protocol Interventions for prevention of herpes simplex labialis (cold sores on the lips) [Chi, 2015], and in international review articles [Raborn and Grace, 2003; Usatine, 2010a; Cunningham, 2012; Stoopler, 2012; Stoopler and Sollecito, 2014].

  • Underlying immunosuppression may increase the risk of recurrent and/or severe infections, and a history of atopic eczema may increase the risk of the complication eczema herpeticum [Lee, 2011].

Oral cancer

  • The information on red flags for oral cancer is based on the National Institute for Health and Care Excellence (NICE) clinical guideline Suspected cancer: recognition and referral [NICE, 2021].

Investigations not usually needed in primary care

  • This recommendation is based on expert opinion in a review article, as the diagnosis is usually made on clinical features alone [Stoopler, 2012].
    • Herpes simplex virus can be detected, and the type determined, using viral culture from skin vesicles. Early in the course of infection, 80–90% of viral cultures from untreated lesions are positive, but the false-negative rate increases 24–48 hours after the lesions have appeared [Usatine, 2010a]. As a result, the diagnostic yield may be poor in people attending primary care. Alternative tests include polymerase chain reaction (PCR), which is a more sensitive method, however these tests are not universally available in primary care.
  • The recommendation to consider arranging investigations for underlying immunosuppression if a person presents with unexplained recurrent episodes which are frequent or severe is based on expert opinion in a review article [Cunningham, 2012], and is also pragmatic, based on what CKS considers to be good clinical practice.

Differential diagnosis

Other conditions that may present similarly include:

  • Herpes simplex labialis (cold sores):
    • Impetigo. For more information, see the CKS topic on Impetigo.
    • Aphthous ulcers — on the inside of the lips. For more information, see the CKS topic on Aphthous ulcer.
    • Chickenpox — lesions occur rarely at the mucocutaneous junction. For more information, see the CKS topic on Chickenpox.
    • Shingles — painful crops of blisters in a dermatomal distribution. For more information, see the CKS topic on Shingles.
    • Stevens-Johnson syndrome — an immune-complex-mediated hypersensitivity disorder that affects the skin and mucous membranes.
    • Syphilis — typically causes a single non-tender ulcer. For more information, see the CKS topic on Syphilis.
    • Behçet syndrome — produces oral and genital ulcerative disease, and may have associated uveitis.
  • Herpes simplex gingivostomatitis:
    • Aphthous ulcers or stomatitis. For more information, see the CKS topic on Aphthous ulcer.
    • Herpangina — small ulcers typically on the soft palate in children, caused by Coxsackie virus.
    • Oral candidiasis. For more information, see the CKS topic on Candida - oral.
    • Glandular fever (infectious mononucleosis). For more information, see the CKS topic on Glandular fever (infectious mononucleosis).
    • Erythema multiforme — a hypersensitivity reaction often triggered by herpes simplex virus that typically produces target-shaped lesions, which may affect the face.
    • Hand, foot, and mouth disease. For more information, see the CKS topic on Hand foot and mouth disease.
    • Shingles — painful crops of blisters in a dermatomal distribution. For more information, see the CKS topic on Shingles.
    • Pharyngitis (for example, streptococcal). For more information, see the CKS topic on Sore throat - acute.
    • Pemphigus vulgaris — rare bullous disease that can cause oral ulcers, cutaneous bullae, and erosions.
    • Bullous pemphigoid — an autoimmune bullous disease that typically affects the elderly.
    • Traumatic lesions (mechanical, thermal, or chemical).
    • Mucositis from chemotherapy or radiation treatment.

Basis for recommendation

The information on the differential diagnoses of herpes simplex labialis and gingivostomatitis is based on expert opinion in review articles [Usatine, 2010b; Stoopler, 2012; George, 2014; BMJ Best Practice, 2021].

Management

Scenario: Herpes labialis (cold sores) and gingivostomatitis

From age 6 months onwards.

When should I refer?

  • Consider admission to hospital if the person:
    • Is unable to swallow due to pain and is at risk of dehydration (especially in children).
    • Is immunocompromised with severe oral herpes simplex infection — they may need intravenous antiviral drug treatment.
    • Has a suspected serious complication of oral herpes simplex infection — they may need intravenous antiviral drug treatment.
  • Arrange a suspected cancer pathway referral (for an appointment within 2 weeks) if there are any red flags suggesting oral cancer.
  • Consider seeking specialist advice or referral to a specialist in infectious diseases or oral medicine, depending on clinical judgement, if the person:
    • Is immunocompromised and has troublesome recurrent oral herpes simplex infection — prophylactic oral antiviral treatment may be needed.
    • Is a pregnant woman (particularly near term) with a primary oral herpes simplex infection — advise the woman that the risk of infecting the neonate by kissing is greatest when a new oral herpes infection is acquired in the third trimester, particularly within 6 weeks of delivery, as protective maternal IgG antibodies will not have had time to develop and cross the placenta and viral shedding may persist in the saliva. 
    • Has frequent (for example, 6 or more episodes in 1 year), persistent, and/or severe episodes of recurrent oral herpes simplex infection — prophylactic oral antiviral treatment may be needed.
    • Has herpes simplex associated with recurrent erythema multiforme — prophylactic oral antiviral treatment may be needed.
    • Has lesions which are refractory to oral antiviral treatment in primary care (if clinically indicated) after 5–7 days.
    • Has atypical lesions or the diagnosis is uncertain.

Basis for recommendation

The recommendations on when to consider admission or referral for a person with oral herpes simplex virus (HSV) infection are largely based on expert opinion in the National Institute for Health and Care Excellence (NICE) clinical guideline Suspected cancer: recognition and referral [NICE, 2021], a Cochrane systematic review Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer [Glenny et al, 2009], international review articles [Cernik et al, 2008; Usatine, 2010a; Williams, 2011; Stoopler, 2012; Straface et al, 2012; Stoopler, 2013; Sawleshwarkar and Dwyer, 2015; BMJ Best Practice, 2021], and a case report [George, 2014].

Considering hospital admission
  • The recommendation on admission if a person is at risk of dehydration and may therefore require intravenous fluids is based on expert opinion in a review article [Esmann, 2001] and is pragmatic based on what CKS considers to be good medical practice.
  • The recommendation on admission if there is a serious complication of oral herpes simplex infection is based on expert opinion in review articles, as intravenous antiviral drug treatment and other specialist intervention may be required [Williams, 2011; PCDS, 2021].
Seeking specialist advice or arranging referral
  • The recommendations relating to people who are immunocompromised with recurrent HSV infection are based on expert opinion in a Cochrane systematic review of people undergoing cancer treatment [Glenny et al, 2009], a review article published by the British HIV Association (BHIVA) [Williams, 2011], review articles on oral herpes simplex infection and antiviral drug treatments [Raborn and Grace, 2003; Usatine, 2010a; Stoopler, 2012; Sawleshwarkar and Dwyer, 2015], and the opinions of previous external reviewers of this CKS topic.
    • People who are immunocompromised are more at risk of severe, prolonged, or frequent recurrent oral disease, and are at increased risk of serious or life-threatening complications [Cunningham, 2012]. They may benefit from episodic or longer-term suppressive oral antiviral drug treatment [Williams, 2011; Stoopler, 2012]. Higher doses or a longer duration of antiviral treatment [Sawleshwarkar and Dwyer, 2015], and/or virological evaluation for antiviral drug resistance may also be required [BMJ Best Practice, 2021].
  • The recommendations relating to pregnant women are based on the well-defined risk of potentially severe or fatal complications that genital HSV infections in pregnancy can pose to the neonate through transmission at the time of delivery if the mother is actively shedding HSV [BASHH, 2014]. Evidence on the risk from maternal oral HSV infections is, however, very limited [Straface et al, 2012], and expert opinion from previous external reviewers of this CKS topic was divided regarding this risk. CKS therefore advises seeking specialist advice for pregnant women with primary HSV infection in the third trimester.
  • The recommendation relating to people with frequent or severe recurrent HSV infections is based on expert opinion in review articles [Cernik et al, 2008; Stoopler, 2012] and a case report [George, 2014] that suppressive oral antiviral treatment may be necessary. The threshold of 6 or more recurrences a year to define frequent infections is based on expert opinion in review articles [Raborn and Grace, 2003; Cernik et al, 2008].
  • The recommendation on referral for people who have HSV complicated by recurrent erythema multiforme is based on expert opinion in review articles [Esmann, 2001; Raborn and Grace, 2003; PCDS, 2021] and in a case report on herpes gingivostomatitis [George, 2014] that suppressive oral antiviral treatment can significantly reduce morbidity associated with recurrent oral infections.
  • The recommendation relating to people with lesions refractory to primary care management is based on expert opinion in a review article that further specialist investigation may be needed to clarify the diagnosis [Stoopler, 2012]. Herpes simplex virus antiviral drug resistance is rare in healthy people (affecting less than 1% of people), but is more common in people who are immunosuppressed (affecting 3.5–10% of people) [Sawleshwarkar and Dwyer, 2015], and this requires specialist management with alternative antiviral agents [Stoopler, 2013].
    • The recommendation to consider referral if there is no clinical improvement after 5–7 days of primary care management is based on the expert opinion of previous external reviewers of this CKS topic, and is pragmatic based on what CKS considers to be good medical practice.
  • The recommendation relating to people with atypical lesions is based on expert opinion in review articles that further specialist investigation with viral culture, cytology, biopsy, or polymerase chain reaction (PCR) assessment may be needed [Usatine, 2010a; Stoopler, 2012], and is pragmatic based on what CKS considers to be good medical practice, as atypical lesions may be more extensive and aggressive than typical lesions, and may be a sign of underlying immunocompromise or immunosuppression.

What drug treatment should I offer for oral herpes simplex infections?

The drug treatment of oral herpes simplex depends on the person's age; the frequency, severity, and distribution of lesions; and the person's immune status.

For people with primary or recurrent herpes labialis or gingivostomatitis infection:

  • Advise the use of paracetamol and/or ibuprofen to treat symptoms of pain and fever, if needed, and there are no contraindications. For prescribing information, see the CKS topics on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues.
  • Do not routinely prescribe topical antiviral preparations, such as aciclovir or penciclovir.
    • These products are available over-the-counter, and may be used by some people if they find them helpful, from the time of onset of prodromal symptoms before vesicles appear, if possible, until lesions have healed.
  • Do not prescribe topical anaesthetic or analgesic preparations, mouthwash, or lip barrier preparations.
    • These products are available over-the-counter, and may be used by some people if they find them helpful. Be aware that some topical analgesic preparations are not licensed for use in children. For further information on contraindications, cautions, drug interactions, and adverse effects of different preparations, see the electronic Medicines Compendium or the British National Formulary.
  • Do not routinely prescribe oral antiviral drug treatment for healthy people with herpes labialis.
  • Consider prescribing oral antivirals for healthy people with an episode of primary oral herpes simplex infection; recurrent herpes labialis if lesions are severe, frequent, or persistent; and recurrent gingivostomatitis (rare), depending on clinical judgement.
  • Consider prescribing oral antivirals for people who are immunocompromised with an episode of primary or recurrent oral herpes simplex infection, depending on clinical judgement.
    • If an oral antiviral drug is indicated, advise the person to take the oral antiviral drug from the time of onset of prodromal symptoms before vesicles appear, if possible, until lesions have healed, for a minimum of 5 days.
    • The choice between the oral antiviral drugs aciclovir or valaciclovir depends on the person's preference, drug cost, dosage regimen, likely adherence, and local prescribing policies. Note: famciclovir is not licensed for the treatment of oral herpes simplex infections. For more prescribing information on recommended drug doses, contraindications and cautions, and adverse effects, see the section on Oral antiviral drugs in the Prescribing information section.
  • If there is concern or uncertainty in the treatment of oral herpes simplex infection, see the section on Referral — long-term oral antiviral prophylaxis may be needed for some people, following specialist advice.

Basis for recommendation

The recommendations on drug treatment of herpes labialis and gingivostomatitis are largely based on expert opinion in a British Medical Journal (BMJ) Clinical Evidence systematic review on herpes labialis [Worrall, 2009], an American Academy of Oral Medicine (AAOM) clinical practice statement Dental care for the patient with an oral herpetic lesion [AAOM, 2016], international review articles [Esmann, 2001; Opstelten, 2008; Usatine, 2010a; Williams, 2011; Stoopler, 2013; Hopper, 2014; Stoopler and Sollecito, 2014; Sawleshwarkar and Dwyer, 2015; Goldman, 2016], and the British National Formulary [BNF, 2021].

Pain relief
  • The recommendation on the use of paracetamol and/or ibuprofen is based on the fact most episodes of herpes labialis and gingivostomatitis are mild and self-limiting, but they can be painful and cause fever and general malaise, which may respond to simple analgesia and antipyretics [Goldman, 2016].
Topical antiviral treatment
  • The recommendation not to routinely prescribe topical antivirals in primary oral herpes simplex infections is based on the fact that CKS found no good-quality evidence from randomized controlled trials (RCTs) that these agents are effective in reducing pain or time to healing compared with placebo or no treatment.
    • A systematic review of interventions to treat primary oral herpes simplex infections noted that relevant data are limited as people tend not to consult healthcare professionals until they have had several episodes of herpes labialis [Worrall, 2009].
  • The recommendation not to routinely prescribe topical antivirals in recurrent herpes labialis infections is based on limited moderate-quality evidence in a systematic review of 12 RCTs of healthy people, comparing topical aciclovir or penciclovir with placebo, which found these agents may reduce pain and healing time, but the results of the studies were inconsistent and of marginal clinical importance [Worrall, 2009]. This is supported by the findings of a US review article on oral herpes simplex infections that topical antiviral treatment has no significant benefit over placebo for healthy people with recurrent herpes labialis [Usatine, 2010a].
Topical anaesthetics, analgesics, mouthwash, and lip barrier preparations
  • The recommendation not to prescribe topical anaesthetics and analgesics, mouthwash, and lip barrier preparations is based on the fact that CKS found no good-quality evidence on the effectiveness of these products for the treatment of herpes labialis, and expert opinion in the literature is conflicting.
    • A systematic review of interventions for recurrent herpes labialis found no RCTs of sufficient quality to make a recommendation on whether topical anaesthetic agents reduce healing time in healthy people [Worrall, 2009].
    • A US randomized placebo-controlled trial (n = 100) of children with acute painful infectious oral ulcers (of various aetiologies) in an emergency department setting found 2% topical lidocaine was not superior to placebo gel in improving oral fluid intake [Hopper, 2014].
    • CKS notes that some topical anaesthetic preparations are available over-the-counter, and expert opinion in an AAOM Clinical practice statement states 'topical anaesthetics, anti-inflammatory agents, and analgesics can help reduce the pain of recurrent herpes lesions' [AAOM, 2016], and expert opinion in a US dental review article recommends their use for some people [Stoopler, 2013].
  • The recommendation on topical lip barrier preparations is based on expert opinion in a US dental review article that they may relieve symptoms for some people [Stoopler, 2013].
    • In addition, expert opinion in a UK case report recommends the use of lip barrier preparations as a simple measure to prevent labial (lip) adhesions, which are a rare but potentially serious complication of herpes gingivostomatitis, which may require surgical intervention if severe [Thomas, 2007].
Prescribing oral antiviral drug treatment
  • The recommendation on not routinely prescribing oral antiviral drugs for healthy people with mild-to-moderate recurrent episodes is based on the fact that most episodes of herpes labialis are self-limiting, the evidence on the benefits of oral antivirals is limited, and oral treatment needs to be initiated at the onset of prodromal symptoms which may be difficult for people in practice.
    • Antiviral drugs inhibit viral replication, and most viral replication occurs within the first 24 hours of infection, so early initiation of treatment limits epithelial damage responsible for the development of clinical herpes simplex lesions [Esmann, 2001; Cunningham, 2012].
  • The recommendation on considering prescribing oral antivirals for healthy people with a primary oral herpes simplex infection is extrapolated from evidence in a systematic review of two small RCTs of healthy children (n = 20 and n = 72) which found limited low-quality evidence that oral aciclovir may reduce the duration of pain and time to healing for a first attack of herpes gingivostomatitis compared with placebo [Worrall, 2009]. This is supported by expert opinion in a US dental review article on the treatment of primary herpes labialis infections [Stoopler, 2013] and a Canadian review article on the use of oral aciclovir for herpes gingivostomatitis in children [Goldman, 2016].
  • The recommendation on considering prescribing oral antivirals for healthy people with persistent, severe, or prolonged episodes of recurrent herpes labialis is based on a systematic review of five RCTs of healthy adults which found that oral aciclovir taken early in a recurrent episode (at the first sign of prodromal symptoms) may be more effective than placebo at reducing symptom duration and healing time. There were, however, no RCTs comparing early versus delayed intervention with oral antiviral agents, therefore the author highlighted it was difficult to draw conclusions about the timing of treatment [Worrall, 2009].
  • The recommendation on considering prescribing oral antivirals in a person who is immunocompromised with primary or recurrent infection is based on expert opinion in a British Medical Journal (BMJ) review article on antiviral drug treatments for herpes simplex virus [Sawleshwarkar and Dwyer, 2015], a review article published by the British HIV Association (BHIVA) [Williams, 2011], and a US review article on oral mucosal diseases [Stoopler and Sollecito, 2014] that these people are more at risk of severe, prolonged, or complicated oral herpes simplex infections.
    • Oral antiviral drugs have comparable efficacy, so drug choice is dependent on patient wishes, drug cost, and the person's likely adherence to the drug regimen [Sawleshwarkar and Dwyer, 2015].

What self-care advice should I give?

Offer the following self-care advice:

  • Reassure the person/carer that oral herpes simplex infections are usually self-limiting, and that lesions should heal without scarring.
  • Advise on measures for symptom relief, such as:
    • Paracetamol and/or ibuprofen to relieve pain and fever, if required, and there are no contraindications.
    • Adequate fluid intake to reduce the risk of dehydration.
    • Topical anaesthetics or analgesics, mouthwash, and lip barrier preparations, which are available over-the-counter, and which some people may find helpful. Be aware that some topical analgesic preparations are not licensed for use in children. For further information on contraindications, cautions, drug interactions, and adverse effects of different preparations, see the electronic Medicines Compendium or the British National Formulary.
  • Give information and advice about the nature and course of oral herpes simplex infections. Offer patient information leaflets, such as:
  • Give advice to minimize the risk of transmission to other people and autoinoculation:
    • Explain that herpes simplex virus is easily transmitted to other people.
    • Avoid kissing and oral sex until all lesions have fully healed.
    • Do not share items that come into contact with lesions (for example makeup and lip balms).
    • Avoid touching the lesions, other than when applying topical preparations, which should be dabbed on rather than rubbed in to minimize mechanical trauma to the lesions. Topical treatments should not be shared with other people.
    • Wash hands with soap and water immediately after touching lesions.
    • Take care if using contact lenses, as there is a risk of transmission to the eye if lenses become contaminated.
    • Defer elective dental treatment until all lesions have fully healed.
  • Inform parents or carers that children with herpes labialis or gingivostomatitis who are well do not need to be excluded from nursery or school.
  • Advise the person to try to avoid trigger factors, if possible.
    • If sunlight is a trigger, advise the use of sunscreen or sunblock lip balm (sun protection factor 15 or greater), to help reduce recurrent episodes.
  • Advise the person/carer to seek medical advice if their symptoms worsen (for example the lesion spreads, new lesions develop, or there is persistent fever or difficulty taking fluids), or no significant improvement is seen after 5–7 days.

Basis for recommendation

The recommendations on self-care advice for people with oral herpes simplex infections are largely based on expert opinion in the American Academy of Oral Medicine (AAOM) clinical practice statement Dental care for the patient with an oral herpetic lesion [AAOM, 2016], international review articles [Esmann, 2001; Usatine, 2010a; Stoopler, 2012; BMJ Best Practice, 2021], and the UK Health Security Agency (UKHSA) document Health protection in schools and other childcare facilities [UKHSA, 2021].

  • Primary herpes labialis lesions usually resolve within 10–14 days of symptom onset without scarring [Usatine, 2010a; Stoopler, 2012].
  • The recommendation on ensuring adequate fluid intake is based on the fact that severe oral pain may cause dehydration requiring hospitalization for intravenous fluids [Esmann, 2001; Goldman, 2016].
  • The recommendation on deferring elective dental treatment until lesions are fully healed is based on the fact that aerosolization of the virus may occur during dental procedures, putting the person and oral healthcare providers at risk [Stoopler, 2012; AAOM, 2016].
  • The recommendation that children with oral herpes simplex infection should not be excluded from nursery or school is based on the UKHSA document Health protection in schools and other childcare facilities [UKHSA, 2021].
  • The recommendation to advise the person to seek medical review if symptoms worsen or do not improve significantly in 5–7 days is based on the expert opinion of previous external reviewers of this CKS topic, and is pragmatic, based on what CKS considers to be good medical practice.

What measures may prevent recurrent oral herpes simplex infection?

  • For people with a history of recurrent oral herpes simplex:
    • If sunlight is a trigger factor, advise the use of sunscreen or sunblock lip balm (sun protection factor 15 or greater), to help reduce recurrent episodes.
    • Advise that the use of oral antiviral prophylaxis is not routinely recommended for healthy people.
    • Advise that the use of topical antiviral prophylaxis is not recommended.
  • Consider seeking specialist advice or arrange referral to a specialist in infectious diseases or oral medicine, depending on clinical judgement, to see whether oral antiviral prophylaxis is appropriate, for people:
    • With a history of frequent, severe, and/or persistent recurrent episodes.
    • Who are immunocompromised with a history of troublesome recurrent oral herpes simplex.
    • Who have herpes simplex associated with recurrent erythema multiforme.

Basis for recommendation

Use of sunscreen to prevent recurrent episodes
  • The recommendation on advising the use of regular sunscreen to prevent recurrent episodes of herpes labialis is based on evidence from:
    • A Cochrane systematic review (search date to May 2015) that found evidence from two randomized controlled trials (RCTs, n =111 in total) that sunscreen application significantly prevented recurrent herpes labialis triggered by ultraviolet light, however a third small RCT (n = 51) found no evidence of clinical benefit from sunscreen application, so the results were inconsistent [Chi, 2015].
    • A smaller British Medical Journal (BMJ) Clinical Evidence systematic review (search date to February 2009) that found limited evidence from two small crossover RCTs (n = 57 in total) that sunscreen may reduce the frequency of recurrent episodes. It was noted that the studies used artificial exposure to ultraviolet light rather than sunlight to trigger herpes labialis episodes, and that both also had methodological limitations due to their crossover design [Worrall, 2009].
    • A randomized crossover study with 20 participants, which found that recurrence of herpes labialis triggered by exposure to sunlight was statistically significantly less likely following use of SPF 30 sunscreen [Mazzarello, 2019].
Topical antiviral agents not recommended
  • The recommendation on not prescribing topical antiviral agents to prevent recurrent episodes of herpes labialis is based on a Cochrane systematic review of two moderate-quality RCTs, which found no evidence that short-term use of topical aciclovir prevented recurrent episodes [Chi, 2015]. This is supported by a BMJ Clinical Evidence systematic review of two low-quality RCTs on the effect of topical aciclovir 5% cream, which found no convincing evidence that this intervention was any more effective than placebo at reducing recurrent episodes, symptoms such as pain, or healing time of recurrent lesions [Worrall, 2009].
Referral for specialist advice on oral antiviral prophylaxis
  • The recommendation on considering referral for specialist advice on prescribing prophylactic oral antiviral drugs for people with frequent, prolonged, and/or severe recurrent oral herpes simplex infections is based on limited evidence from two systematic reviews of healthy people.
    • A Cochrane systematic review (search date to May 2015) of 32 RCTs (n = 2640) found that there was conflicting evidence on the benefit of short-term (less than 1 months' duration) oral aciclovir (using different study doses) in reducing recurrence rates. In contrast, longer-term (more than 1 months' duration) use of oral aciclovir and valacyclovir reduced the clinical recurrence rate, but it produced a very small reduction of 0.09 episodes per person per month. Overall, oral antiviral agents can prevent recurrent episodes, but the clinical benefit is small [Chi, 2015].
    • A smaller BMJ Clinical Evidence systematic review (search date to February 2009) of five RCTs of interventions to prevent recurrent episodes of herpes labialis found some evidence that prophylactic use of oral aciclovir and valaciclovir may reduce the number of recurrent episodes compared with placebo. The studies were, however, largely old, showed significant heterogeneity (using different antiviral drug regimens, population groups, and triggers for episodes), and overall were of limited methodological quality [Worrall, 2009].
  • The recommendation on considering referral for people who are immunocompromised with recurrent oral herpes simplex infections is based on a Cochrane systematic review (search date to November 2008) of 12 RCTs of people receiving cancer treatment, which found oral aciclovir was effective in preventing oral herpes simplex clinical lesions. This population group is at increased risk of serious and life-threatening complications from oral herpes simplex infections [Glenny et al, 2009].
  • The recommendation on considering referral for people with herpes simplex infections complicated by recurrent erythema multiforme is based on expert opinion in review articles [Esmann, 2001; Raborn and Grace, 2003; PCDS, 2021] and a case report on herpes gingivostomatitis [George, 2014] that long-term suppressive oral antiviral treatment can significantly reduce morbidity associated with recurrent oral infections.
  • CKS has therefore not routinely recommended the use of prophylactic oral antivirals for people with recurrent episodes in primary care, due to the limited evidence of benefit, but recommends considering referral for a specialist opinion.

Prescribing information

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (emc) or the British National Formulary.

Analgesia

Paracetamol and ibuprofen

Oral antiviral drugs

Oral antiviral drugs are indicated within 5 days of the start of the episode, while new lesions are still forming, or if systemic symptoms persist.

Aciclovir is licensed for the treatment of herpes simplex infections of the skin and mucous membranes, including oral herpes gingivostomatitis. Advise that it should be started at the onset of any prodromal symptoms or signs.

  • Adults and children aged 2–18 years — prescribe aciclovir 200 mg five times daily. Prescribe a longer course, depending on clinical judgement, if new lesions appear during treatment, or if healing is incomplete.
  • Children aged 1 month to under 2 years — prescribe 100 mg five times a day (usually every 4 hours while awake) for 5 days. Prescribe a longer course, depending on clinical judgement, if new lesions appear during treatment, or if healing is incomplete.
  • Immunocompromised people — prescribe double the standard doses for healthy people.

Valaciclovir is licensed for the treatment of herpes simplex infections of the skin and mucous membranes. Advise it should be started at the onset of any prodromal symptoms or signs.

  • Adults and children aged 12 years and over — prescribe 500 mg twice a day for 5 days for primary infections, which may be extended to 10 days if new lesions appear during treatment, or if healing is incomplete. Prescribe 500 mg twice a day for 3–5 days for recurrent episodes. An alternative regime for herpes labialis is 2000 mg twice a day for 1 day only. The second dose should be taken about 12 hours after the first dose.
  • Immunocompromised people — prescribe 1000 mg twice a day for up to 10 days for primary infections, and for 5–10 days for recurrent episodes.
  • Note: valaciclovir is not licensed for use in children under 12 years of age.

[ABPI, 2020; ABPI, 2021; BNF, 2021]

Adverse effects

  • Aciclovir and valaciclovir are generally well tolerated.

    • They may cause headaches, fatigue, dizziness, nausea, vomiting, diarrhoea, abdominal pain, itch, and rash (including photosensitivity and urticaria).
    • Valaciclovir has been reported to cause tubulointerstitial nephritis. 

[ABPI, 2020; ABPI, 2021; BNF, 2021; ABPI, 2023 Valtrex 500mg tablets]

Contraindications and cautions

  • Do not prescribe aciclovir to a person with a known hypersensitivity to aciclovir, valaciclovir, or any of the expients.
  • Prescribe aciclovir with caution to a person who:
    • Is elderly — dose reduction may be needed depending on risk of renal impairment.
    • Has an underlying neurological abnormality.
    • Has severe liver or electrolyte abnormalities.
    • Has significant hypoxia.
    • Has renal impairment — advise the person to maintain adequate fluid intake, as aciclovir is eliminated by renal clearance. Reduce the dose to 200 mg every 12 hours if the estimated glomerular filtration rate (eGFR) is less than 10 mL/min/1.73 m2.
    • Is breastfeeding — aciclovir has been detected in breast milk when given at oral doses to treat herpes simplex infections. It is not known to be harmful, but the manufacturer advises caution.
  • Do not prescribe valaciclovir to a person with a known hypersensitivity to valaciclovir.
  • Prescribe valaciclovir with caution to a person who:
    • Is elderly — dose reduction may be needed depending on risk of renal impairment.
    • Has hepatic impairment.
    • Has renal impairment — advise the person to maintain adequate fluid intake.
      • If the eGFR is 30–50 mL/min/1.73 m2, prescribe 1000 mg initially, then 1000 mg 12 hours later.
      • If the eGFR is 10–30 mL/min/1.73 m2, prescribe 500 mg initially, then 500 mg 12 hours later.
      • If the eGFR is less than 10 mL/min/1.73 m2, prescribe 500 mg as a single dose.
    • Is breastfeeding — valaciclovir has been detected in breast milk when given at oral doses to treat herpes simplex infections. It is not known to be harmful, but the manufacturer advises caution.

[ABPI, 2020; ABPI, 2021; BNF, 2021]

Drug interactions

  • No clinically significant drug interactions have been reported for aciclovir and valaciclovir, but the following have been reported as possible drug interactions:
    • The risk of renal impairment is increased by the concomitant use of other nephrotoxic drugs with aciclovir or valaciclovir.
    • Aminophylline and theophylline — aciclovir or valaciclovir may increase plasma aminophylline and theophylline levels.
    • Ciclosporin — increased risk of nephrotoxicity when aciclovir or valaciclovir is given with ciclosporin.
    • Mycophenolate — plasma concentration of aciclovir or valaciclovir increased by mycophenolate.
    • Tacrolimus — possible increased risk of nephrotoxicity when aciclovir or valaciclovir is given with tacrolimus.

[ABPI, 2020; ABPI, 2021; BNF, 2021]

Supporting evidence

This CKS topic is largely based on expert opinion in international review articles on oral herpes simplex and antiviral drug treatments. The rationale for the individual recommendations is discussed in the relevant basis for recommendation sections. CKS has not summarized the evidence for secondary care investigations and management as they are beyond the scope of this topic.

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of herpes simplex oral.

Search dates

September 2012 - September 2021

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

  •  exp herpes simplex oral/
  •  exp Herpesvirus 1, Human/
  • exp Herpes Labialis/
  • exp Herpes Simplex/
  • exp Stomatitis, herpetic/
  • Herpetic Gingivostomatitis.kw.
  • (treatment or prevent$) adj3 (herpes labialis).ti,ab.
  • (Oral or perioral) adj3 (herpes simplex).ti,ab.
  • Orolabial adj (herpes or infection).ti,ab.
  • “herpes simplex virus”or “herpes labialis” or “recurrent herpes labialis” or RHL or “cold sore”.ti,ab.

Sources of guidelines

Sources of systematic reviews and meta-analyses

  • The Cochrane Library:
    • Systematic reviews
    • Protocols
    • Database of Abstracts of Reviews of Effects
  • Medline (with systematic review filter)
  • EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

Sources of randomized controlled trials

  • The Cochrane Library:
    • Central Register of Controlled Trials
  • Medline (with randomized controlled trial filter)
  • EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Sources of national policy

Patient experiences

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

  • Clinical accuracy.
  • Consistency with other providers of clinical knowledge for primary care.
  • Accuracy of implementation of national guidance (in particular NICE guidelines).
  • Usability.

Principles of the consultation process

  • The process is inclusive and any individual may participate.
  • To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
  • Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
  • Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
  • External reviewers are not paid for commenting on the draft topics.
  • Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
  • All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
  • All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

  • Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
  • Stakeholders identified from the following groups are invited to review draft topics:
    • Experts in the topic area.
    • Professional organizations and societies (for example, Royal Colleges).
    • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
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    • The British National Formulary team.
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Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

  • Topic selection
  • Scoping of topic
  • Selection of clinical scenarios
  • First draft internal review
  • Second draft internal review
  • External review
  • Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
    • Likely uptake of new intervention or recommendation
    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
  • Personal family interest
  • Personal non-financial interest
  • Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.

References

  • AAOM (2016) Dental Care for the Patient with an Oral Herpetic Lesion. American Academy of Oral Medicine.. www.aaom.com/ [Free Full-text]
  • ABPI (2020) SPC for Aciclovir 200 mg tablets. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • ABPI (2021) SPC for Valaciclovir 500 mg Film Coated Tablets. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • ABPI (2023) SPC for Valtrex 500mg tablets. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc
  • Ahluwalia, J., Han, A., Kusari, A. and Eichenfield, L.F. (2019) Recurrent herpes labialis in the pediatric population: prevalence, therapeutic studies, and associated complications. Pediatric Dermatology 36(6), 808-814. [Abstract]
  • BASHH and RCOG (2014) Management of genital herpes in pregnancy. British Association for Sexual Health and HIV and the Royal College of Obstetricians and Gynaecologists. http://www.rcog.org.uk [Free Full-text]
  • Bentley, J.M., Barankin, B. and Guenter, L.C. (2003) A review of common pediatric lip lesions: herpes simplex/recurrent herpes labialis, impetigo, mucoceles, and hemangiomas. Clinical Pediatrics 42(6), 475-482. [Abstract]
  • BMJ Best Practice (2021) Herpes simplex virus infection. London: BMJ Publishing group.
  • BNF (2021) British National Formulary. BMJ Group and Pharmaceutical Press. https://bnf.nice.org.uk
  • Cernik, C., Gallina, K. and and Brodell, R. (2008) The treatment of herpes simplex infections: an evidence-based review. Archives of internal medicine. 168(11), 1137-1144. [Abstract]
  • Chi, C., Wang, S. and Delamere, F. (2015) Interventions for prevention of herpes simplex labialis (cold sores on the lips) (Cochrane Review). Issue 8. John Wiley & Sons, Ltd. http://www.cochranelibrary.com [Free Full-text]
  • Cunningham, A., Griffiths, P. and Leone, P. (2012) Current management and recommendations for access to antiviral therapy of herpes labialis. Journal of Clinical Virology 53(1), 6-11. [Abstract]
  • Esmann, J. (2001) The many challenges of facial herpes simplex virus infection. Journal of Antimicrobial Chemotherapy 47(Suppl T1), 17-27. [Abstract]
  • Fatahzadeh, M. and Schwartz, R.A. (2007) Human herpes simplex labialis. Clinical and Experimental Dermatology 32(6), 625-630. [Abstract]
  • George, A. and Anil, S. (2014) Acute herpetic gingivostomatitis associated with herpes simplex virus 2: report of a case. Journal of International Oral Health 6(3), 99-102. [Abstract]
  • Glenny, A., Fernandez-Mauleffinch, L., Pavitt, S. and and Walsh, T. (2009) Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer (Cochrane Review). John Wiley & Sons, Ltd.. www.cochranelibrary.com/ [Free Full-text]
  • Goldman, R. (2016) Acyclovir for herpetic gingivostomatitis in children. Canadian Family Physician. 62(5), 403-404. [Free Full-text]
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