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Oral health

Aphthous ulcer

Last revised in March 2024

Aphthous ulcers are painful, clearly defined, round or ovoid, shallow ulcers that are confined to the mouth and not associated with systemic disease

Aphthous ulcer: Summary

  • Aphthous ulcers are painful, clearly defined, round or ovoid, shallow ulcers that are confined to the mouth and are not associated with systemic disease. They are often recurrent, with onset usually in childhood.
  • Single ulcers, or recurrent ulcers in the same place, may be caused by damage to the mouth, for example biting the cheek, or damage to the buccal mucosa with a toothbrush, sharp tooth, or filling.
  • People with recurrent ulcers may have a genetic predisposition.
  • Various factors have been suggested to precipitate recurrent aphthous ulcers including:
    • Oral trauma.
    • Anxiety or stress.
    • Certain foods (including chocolate, coffee, peanuts, and gluten-containing products).
    • Vitamin and mineral deficiencies.
    • Stopping smoking.
    • Hormonal changes related to the menstrual cycle.
  • Investigations are generally unnecessary. However, a full blood count and measurement of erythrocyte sedimentation rate, ferritin, folate, and vitamin B12 should be arranged if an underlying systemic disease is suspected as the cause of oral ulceration.
  • Most aphthous ulcers heal within 10–14 days without scarring.
  • Management of aphthous ulcers includes:
    • Avoidance of precipitating factors, and
    • Symptomatic treatment for pain, discomfort, and swelling, for example, a short course of a low potency topical corticosteroid, an antimicrobial mouthwash, or a topical analgesic.
  • People with a single mouth ulcer that persists for more than 3 weeks should be referred urgently to a specialist for biopsy to rule out malignancy.

Have I got the right topic?

From age 5 years onwards.

This CKS topic covers the management of aphthous ulcers. These are also known as aphthous stomatitis, aphthae, or canker sores.

This CKS topic does not cover the management of ulceration due to infection with the herpes simplex virus, or ulcers due to other causes.

There are separate CKS topics on Crohn's disease, Herpes simplex - oral (which includes cold sores), Hand foot and mouth disease, and Palliative care - oral.

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

March 2024  — minor update. Adverse effects of doxycycline updated in line with the manufacturer's SPC.

Previous changes

April 2022 — reviewed. A literature search was conducted in March 2022 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.

April 2021 — minor update. A typographical error has been corrected.

March to April 2017 — reviewed. A literature search was conducted in March 2017 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made.

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 changes to clinical recommendations have been made.

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

August 2009 — minor update. Triamcinolone in an adhesive paste (Adcortyl in Orabase®) is no longer available in either the 5 gram or the 10 gram pack size. Prescription removed. Issued in August 2009.

August to November 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. There are no major changes to the recommendations.

October 2005 — minor technical update. Issued in November 2005.

July 2005 — updated to incorporate the Referral guidelines for suspected cancer published by the National Institute for Health and Care Excellence. Issued in July 2005. 

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

April 2002 — rewritten, replacing guidance called Aphthous stomatitis. Validated in June 2002 and issued in July 2002.

September 1998 — written.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 April 2022.

HTAs (Health Technology Assessments)

No new HTAs since 1 April 2022.

Economic appraisals

No new economic appraisals relevant to England since 1 April 2022.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 April 2022.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 April 2022.

New policies

No new national policies or guidelines since 1 April 2022.

New safety alerts

No new safety alerts since 1 April 2022.

Changes in product availability

No changes in product availability since 1 April 2022.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

  • Make a diagnosis of aphthous ulcer.
  • Offer advice on relieving symptoms.
  • Offer treatment where appropriate.
  • Refer appropriately if malignancy is suspected.

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

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

NICE quality standards

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

Background information

What is it?

  • Aphthous ulcers are erythematous, small, round, or ovoid oral ulcers with circumscribed margins, typically presenting first in childhood or adolescence, and not associated with systemic disease.
  • Aphthous ulcers are often recurrent, with a natural history of spontaneous resolution with age.
  • Aphthous ulcers occur in three different clinical morphological variants that can occasionally occur simultaneously.
    • Minor ulcers are less than 1 cm in diameter (usually 2–5 mm) and heal spontaneously in less than 14 days. They account for around 85% of all recurrent oral aphthous ulcers.  
    • Major ulcers are usually 1–3 cm in diameter, deeply indurated, and can last for 10 days to 6 weeks or occasionally even longer. They account for around 10% of recurrent benign oral ulcers.
    • Herpetiform aphthous ulcers are very small (1–2 mm) grouped lesions. They account for around 5% of aphthous ulcers, are extremely painful, and persist for 7–10 days. As many as 100 ulcers can be present and they may coalesce into larger erosive plagues. 

[BMJ Best Practice, 2018; Manfredini, 2021]

How common is it?

  • Recurrent aphthous ulceration is seen worldwide and may affect up to 25% of the population.
  • Prevalence of oral ulcers in children has been reported as 9% [Legeret, 2021]. Aphthous ulceration was the commonest pathology found on biopsy [Hong, 2019].
  • Aphthous ulcers are more common in:
    • Women.
    • People under 40 years of age.
    • Non-smokers.
    • People of high socioeconomic status.
    • Data from the US suggest ulcers are 3 times more common in white people than in black people.

[BMJ Best Practice, 2018]

What causes it?

  • Possible causes of aphthous ulceration include:
    • Genetic predisposition — a positive family history can be found in up to 40% of people. The likelihood of ulcers in a child when both parents have ulcers is 90%, but only 20% if neither parent has ulcers [BMJ Best Practice, 2018].
    • Smoking cessation.
    • Iron, zinc, folic acid, vitamin B group, or vitamin D deficiency [Al-Maweri, 2019; Yildirimyan, 2019; Al-Maweri, 2021].
    • Hormonal factors — in some women, ulcers coincide with the luteal phase of the menstrual cycle and may remit with oral contraceptives or during pregnancy [Tarakji, 2015].
    • Local trauma to the oral mucosa (for example, caused by sharp and/or broken teeth, dentures and orthodontic appliances, and biting during chewing). 
    • Anxiety.
    • Exposure to certain foods (typically chocolate, coffee, peanuts, and/or gluten products).

[Saikaly, 2018]

What are the complications and prognosis?

  • Secondary bacterial infection is a potential, but uncommon, complication.
  • Minor aphthous ulcers typically heal within 10–14 days without scarring.
  • Major aphthous ulcers may take several weeks to heal and often leave a scar.
  • Herpetiform aphthous ulcers usually heal in 10–14 days.
  • Many people have infrequent recurrences (once or twice a year), but some have almost continuous disease activity. Disease activity tends to decrease over time.

[Tarakji, 2015; BMJ Best Practice, 2018; Manfredini, 2021]

Diagnosis of aphthous ulcer

When should I suspect aphthous ulcer?

  • Examine the person's oral cavity:
    • Minor aphthous ulcers typically present as small round or ovoid ulcers of 2–4 mm in diameter, occur in groups of up to 6 at a time, and are found mainly on the non-keratinized mucosa of the lips, cheeks, floor of the mouth, sulci, or ventrum of the tongue. They heal in 7–10 days, and recur at intervals of 1–4 months, usually leaving little or no evidence of scarring. They represent 75–85% of all aphthous ulcers.
    • Major aphthous ulcers are around 1 cm in diameter or larger, occur in groups of up to 6 at a time, and involve any oral site, including the keratinized mucosa (palate and dorsum of tongue). They are often more painful and persistent, healing slowly over 10–40 days. They often scar and may recur frequently. They represent 10–15% of all aphthous ulcers.
    • Herpetiform aphthous ulcers (uncommon) present as multiple pinhead-sized discrete ulcers that increase in size and coalesce to leave large areas of ulceration. They are often extremely painful and can involve any oral site, including the keratinized mucosa (palate and dorsum of tongue). They heal in 10 days or longer and may recur so frequently that ulceration seems continuous.
    • Assess for the presence of local trauma as an underlying cause (for example from sharp and/or broken teeth, dentures and orthodontic appliances, and biting during chewing).
  • Ask about:
    • The duration of the ulceration. 
      • Note: any solitary ulcer that has persisted for 3 weeks or longer may represent an oral malignancy and warrants urgent referral for biopsy.
    • Family or personal history of oral ulceration:
      • Over 40% of people with aphthous ulcers have first-degree relatives with the condition.
      • The onset of aphthous ulcer is usually during childhood and in 80% of cases, is before 30 years of age.
    • Smoking status:
      • Aphthous ulceration is more common in non-smokers.
  • Be aware that oral ulceration similar in clinical appearance to aphthous ulceration can present as a manifestation of a number of systemic disorders (for more information see the section on Differential diagnosis). Aphthous ulcer may be the most likely diagnosis in a person who is afebrile, with no history of genital or ocular ulceration, or immunodeficiency, and in the absence of pallor.
  • If the diagnosis is uncertain, consider arranging:
    • A full blood count (to rule out anaemia).
    • Measurement of serum ferritin, folate, vitamin B12 (to rule out deficiencies).
    • An immunoglobulin A-tissue transglutaminase (IgA-tTG) test (in case of coeliac disease).
    • Viral serology (to rule out HIV or EBV infection).
    • Measurement of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (to rule out systemic inflammatory disease such as Behcet's syndrome).

Basis for recommendation

The recommendations on diagnosis of aphthous ulcer are based on a Guideline for the diagnosis and treatment of recurrent aphthous stomatitis for dental practitioners [Tarakji, 2015] and also on expert opinion in a BMJ Best Practice review article Oral aphthous ulcers [BMJ Best Practice, 2018].

What else could it be?

The differential diagnoses of aphthous ulcers include:

  • Oral malignancy. Suspect if the person has:
    • A solitary ulcer or swelling of the oral mucosa persisting for more than 3 weeks. 
      • Early lesions are often asymptomatic and appear as areas of erythroplakia (red patch) or leukoplakia (white patch) and may be ulcerated or exophytic (growing outwards). As the lesion grows it becomes more symptomatic.
    • Cervical lymphadenopathy may also be present.
    • The level of suspicion should be increased in the presence of smoking, alcohol misuse, age over 45 years, and male sex. Other forms of tobacco use and chewing betel, gutkha, or paan, should also raise suspicion.
    • For more information, see the CKS topic on Head and neck cancers - recognition and referral.
  • Aphthous-like ulcers resemble recurrent aphthous ulcers in their physical characteristics but are associated with an underlying systemic disorder. Consider an underlying condition if the ulcers first occur later in life, affect atypical sites in the mouth (such as the palate or gums), also affect extra-oral sites (such as genitalia), or are associated with systemic features.
    • Systemic conditions that present with aphthous-like ulcers include:
      • Vitamin B12 deficiency — suspect if the person has peripheral neuropathy or posterior column degeneration (for example ataxia). Pallor, fatigue, weakness, decreased exercise tolerance, and shortness of breath with exercise may be caused by the resulting anaemia. 
      • Folate deficiency — suspect if the person has history of a diet poor in sources of folate, or of heavy alcohol use. Pallor, fatigue, weakness, decreased exercise tolerance, and shortness of breath with exercise may be caused by the resulting anaemia.
      • Iron deficiency — suspect if the person has glossitis, angular stomatitis, and spooning of the nails. Pallor, fatigue, weakness, decreased exercise tolerance, and shortness of breath with exercise may result from anaemia.
      • Coeliac disease — suspect if the person has unexplained gastrointestinal symptoms, chronic diarrhoea, unexplained iron deficiency anaemia, or a skin rash consistent with dermatitis herpetiformis.
      • Crohn's disease — suspect if the person has bloody diarrhoea, weight loss, labial or facial swelling, and occasionally, joint manifestations. Be aware that symptoms can be highly variable.
      • Ulcerative colitis — suspect if the person has left-sided abdominal pain and bloody diarrhoea.
      • Behçet's syndrome — suspect if the person has genital ulcers, uveitis, or retinal damage, skin lesions such as erythema nodosum, papulopustular lesions, and acneform nodules.
      • Reiter's syndrome (reactive arthritis) — suspect if the person has an asymmetrical large joint oligoarthritis with or without dactylitis, urethritis, and ocular inflammation manifesting 1–6 weeks after an acute infection.
      • Immunodeficiency, such as neutropenia, HIV infection — suspect if the person has recurrent fever and recurrent infections or other clinical evidence of risk factors for HIV infection.
      • Epstein-Barr virus infection (glandular fever) — suspect if the person has other features of glandular fever.
      • For more information, see the CKS topics on Anaemia - B12 and folate deficiency, Anaemia - iron deficiency, Coeliac disease, Crohn's disease, Ulcerative colitis, HIV infection and AIDS, and Glandular fever (infectious mononucleosis).
  • Other differential diagnoses include:
    • Primary oral herpes simplex infection — may be asymptomatic, but may present as gingivostomatitis (inflammation of the gums and mucous membranes of the mouth) and pharyngitis. For more information, see the CKS topic on Herpes simplex - oral.
    • Intraoral secondary herpes simplex (cold sores) — can present as a small crop of pinhead-sized ulcers that re-occur at the same site within the mouth, often on keratinized, particularly palatal, oral mucosa. For more information, see the CKS topic on Herpes simplex - oral.
    • Adverse drug reactions (for example to nonsteroidal anti-inflammatory drugs, nicorandil, or beta-blockers) — there may be a temporal relationship to starting or increasing the dose of the drug.
    • Chickenpox — associated skin lesions are present. For more information, see the CKS topic on Chickenpox.
    • Hand, foot, and mouth disease — blister-like lesions may also be seen on hands or feet. For more information, see the CKS topic on Hand foot and mouth disease.
    • Periodic syndrome, PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) — although rare, this tends to occur in young children.

Basis for recommendation

The information on the differential diagnoses of aphthous ulcer is based on expert opinion in the National Institute for Health and Care Excellence (NICE) guideline Suspected cancer: recognition and referral [NICE, 2021], the Primary Care Dermatology Society guideline Oral lesions and other dermatological conditions of the mouth [Primary Care Dermatology Society, 2016], the Guideline for the diagnosis and management of recurrent aphthous stomatitis for dental practitioners [Tarakji, 2015], and in the BMJ Best Practice review article Oral aphthous ulcers [BMJ Best Practice, 2018].

Management

Scenario: Management of aphthous ulcer

From age 5 years onwards.

How should I manage a person with aphthous ulcer?

  • If symptoms and signs and/or the results of preliminary tests suggest an underlying cause for oral ulceration, refer for specialist assessment, with urgency determined using clinical judgement, or treat the identified condition in primary care where appropriate.
  • If aphthous ulcer is suspected:
    • Advise the person about avoiding 'trigger factors' including oral trauma and certain foods and drinks (such as coffee, chocolate, peanuts, and gluten-containing products). Avoiding toothpaste containing sodium lauryl sulfate may be beneficial.
      • For all people with local trauma (for example from sharp and/or broken teeth, dentures and orthodontic appliances, and biting during chewing) appropriate dental treatment should be advised.
    • Offer the person information on the natural history of aphthous ulcer. Patient information leaflets are available from the British and Irish Society for Oral Medicine.
    • Depending on the severity of the person's symptoms, consider offering medication to achieve pain relief, reduction of ulcer duration, and reduction in frequency of episodes. 
      • If ulcers are infrequent, mild, and not interfering with daily activities (for example eating), treatment may not be needed.
      • Simple therapies that can be used alone or in addition include topical anaesthetics such as lidocaine, topical analgesic/anti-inflammatory agents such as benzydamine, and topical antimicrobial agents such as chlorhexidine gluconate oral solution, or doxycycline rinses. There is some evidence that some herbal treatments and probiotics may help to reduce the pain associated with recurrent aphthous ulcers.
      • If these are insufficient, first-line treatment is usually a topical corticosteroid such as hydrocortisone oromucosal tablets, beclomethasone spray (delivered via an inhaler device — off-license use), or betamethasone soluble tablets. Duration of treatment is decided on a case-by-case basis.
      • For people with severe recurrent aphthous ulceration, a short course of systemic prednisolone can be prescribed.
      • Consider prescribing or advising the use of an oral vitamin B12 (cyanocobalamin) supplement, irrespective of serum vitamin B12 levels.
      • For more information, see the section on Prescribing information.
    • Consider specialist referral if ulceration is severe and does not respond to topical treatments or systemic corticosteroids.

Basis for recommendation

The recommendations on management of a person with aphthous ulcer are largely based on expert opinion in the guideline Diagnosis and management of recurrent aphthous stomatitis for dental practitioners [Tarakji, 2015] and review articles [Scully, 2016; BMJ Best Practice, 2018; Manfredini, 2021].

Referral or treatment of people with underlying conditions
  • The recommendation to refer people with suspected underlying conditions with urgency determined by clinical judgement, or to treat in primary care if appropriate, is pragmatic, based on what CKS considers to be good medical practice.
Toothpaste type
  • A 2019 systematic review (n = 124 patients) suggested that people with recurrent aphthous stomatitis may benefit from using sodium lauryl sulfate-free toothpaste [Alli, 2019].
Probiotics and herbal supplements
  • A 2020 systematic review found seven randomized controlled trials looking at the efficacy of probiotics to treat aphthous ulcers. The results were mixed but did show a reduction in pain when probiotics were used versus placebo [Cheng, 2020].
  • 2021 and 2022 systematic reviews found 33 articles for analysis and reported herbal treatments result in lower pain and reduced ulcer size [Srivastava, 2021; Shavakhi, 2022].
Recommended treatments
  • The information on the specific preparations of topical corticosteroids, and anti-inflammatory and anti-bacterial solutions recommended for the treatment of aphthous ulcer is from the British National Formulary [BNF, 2022].
  • A 2020 systematic review and meta-analysis (although not conclusive) suggested a single application of topical doxycycline was beneficial in reducing healing time [Al-Maweri, 2020].
Vitamin B12 prescription
  • The recommendation to consider prescribing vitamin B12 even where serum levels (if measured) are within the normal range is based on information from studies which have demonstrated evidence of benefit from vitamin B12 in the absence of deficiency [Scully, 2016; BMJ Best Practice, 2018].
  • A 2021 systematic review and meta-analysis of 16 studies involving 1534 patients showed that vitamin B12 treatment resulted in a shorter duration of treatment and lower recurrence rate [Shi, 2021].
Specialist referral if ulceration is severe and does not respond to topical treatments or systemic corticosteroids
  • This recommendation is based on information that thalidomide, immune modulatory or low-level laser treatment may be an appropriate treatment for people with severe aphthous ulceration who have not responded to other therapies, and specialist supervision would therefore be required [Scully, 2016; BMJ Best Practice, 2018; Khaleel Ahmed, 2020; Manfredini, 2021].

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 (BNF).

Beclometasone dipropionate

  • Beclometasone dipropionate is used off-license in the treatment of aphthous ulcer in adults.
  • An inhaler device is used to spray the product onto the oral mucosa.
  • The recommended dose is 50–100 micrograms, twice daily.
  • For detailed information on the contraindications and cautions, adverse effects, and drug interactions for beclometasone dipropionate, please see the CKS topic on Corticosteroids - inhaled.

Betamethasone soluble tablets

Dose

For children aged 12 years and over, and adults:

  • 500 micrograms, 4 times a day, to be dissolved in 20 mL water and rinsed around the mouth. Not to be swallowed.

[BNF, 2022]

Adverse effects

Adverse effects of topical betamethasone include:

  • Candidal infection.
  • Exacerbation of local infection.

[BNF, 2022]

Contraindications and cautions

Do not prescribe betamethasone soluble tablets to people with untreated local (oral) infections.

[BNF, 2022]

Drug interactions

No drug interactions are expected with topically administered betamethasone.

Hydrocortisone oromucosal tablets

Dose

Children and adults:

  • 1 lozenge, four times a day, allowed to dissolve slowly in the mouth in contact with the ulcer.

[BNF, 2022]

Adverse effects

Adverse effects of hydrocortisone oromucosal tablets include:

  • Candidial infection.
  • Exacerbation of local infection.
  • Hypersensitivity reactions.

[BNF, 2022]

Contraindications and cautions

Do not prescribe hydrocortisone oromucosal tablets to people with untreated local (oral) infections.

[BNF, 2022]

Drug interactions

There are no known drug interactions with hydrocortisone oromucosal tablets.

[BNF, 2022]

Oral prednisolone

For detailed prescribing information on oral prednisolone, please see the CKS topic on Corticosteroids - oral.

Benzydamine hydrochloride

Dose

Mouthwash:  

  • Children aged 13 years and over, and adults — rinse 15 mL every 1.5 to 3 hours as required. Dilute with an equal volume of water if stinging occurs.

Oromucosal spray: 

  • Children 1 month to 5 years — 1 spray to the affected area every 1.5 to 3 hours (maximum per dose, 4 sprays every 1.5 to 3 hours), 1 spray per 4 kg body weight.
  • Children 6 to 11 years — 4 sprays to the affected area every 1.5 to 3 hours.
  • Children 12 years and over, and adults — 4 to 8 sprays to the affected area every 1.5 to 3 hours.

[BNF, 2022]

Adverse effects

  • The most common adverse effect of benzydamine hydrochloride is oral numbness or stinging.
  • Other adverse effects of benzydamine hydrochloride include:
    • Hypersensitivity reactions which may be associated with pruritus, urticaria, photosensitivity reaction, and rash.
    • Laryngospasm or bronchospasm.
    • Angioedema.
    • Anaphylactic reactions.

[ABPI, 2017; BNF, 2022]

Contraindications and cautions

Do not prescribe benzydamine hydrochloride to:

  • Pregnant women.
  • People with known hypersensitivity to any of the ingredients.

Prescribe benzydamine hydrochloride with caution to:

  • Breastfeeding women.

[ABPI, 2017]

Drug interactions

There are no known drug interactions for topical benzydamine hydrochloride, although systemic absorption has been known to follow topical application of nonsteroidal anti-inflammatory drugs so the possibility of interactions should be considered.

[ABPI, 2017; BNF, 2022]

Chlorhexidine

Dose

Mouthwash:

  • Children and adults — rinse 10 mL twice daily for about 1 minute.

Dental gel:

  • Children and adults — apply up to twice daily to affected areas.

Oromucosal spray:

  • Children and adults — apply up to 12 sprays twice daily to affected areas.

[BNF, 2022]

Adverse effects

Adverse effects of chlorhexidine use include:

  • Mucosal irritation — if desquamation occurs, discontinue treatment or advise dilution of mouthwash with an equal volume of water.
  • Parotid gland swelling.
  • Reversible brown staining of teeth or dentures.
  • Taste disturbance.
  • Tongue discolouration.

[BNF, 2022]

Contraindications and cautions

Do not prescribe chlorhexidine mouthwash, dental gel, or oromucosal spray to people who have previously exhibited hypersensitivity to any of the ingredients. Avoid contact with the eyes and middle ear.

[BNF, 2022]

Drug interactions

  • There are no known drug interactions with chlorhexidine.
  • However, chlorhexidine is incompatible with anionic agents (found in toothpaste). Advise the person to rinse the mouth thoroughly with water in between using toothpaste and a chlorhexidine-containing product.

[ABPI, 2016a; BNF, 2022]

Doxycycline rinses

Dose

Children aged 12 years and older, and adults:

  • 100 mg, 4 times a day. Stir the dispersible tablet into a small amount of water, rinse around the mouth for 2–3 minutes, preferably do not swallow.

[BNF, 2022]

Adverse effects

  • Blood disorders — haemolytic anaemia, thrombocytopenia, neutropenia, eosinophilia (rare).
  • Gastrointestinal — nausea, vomiting, diarrhoea (common), dyspepsia (uncommon). Abdominal discomfort, tooth discolouration, and enamel hypoplasia in children (frequency unknown).
    • Rarely: dysphagia, oesophagitis, oesophageal irritation, pseudomembranous colitis. For more information, see the CKS topic on Diarrhoea - antibiotic associated. (Advice to swallow the capsules with plenty of water, in an upright position, and well before going to bed helps to reduce the frequency of oesophagitis and oesophageal ulceration.)
  • Immune system disorders – hypersensitivity common (including anaphylaxis, angioedema, exacerbation of systemic lupus erythematosus, Henoch-Schonlein purpura). Rarely drug reaction with eosinophilia and systemic symptoms (DRESS).
  • Hepatic disorders – hepatotoxicity, hepatitis, jaundice, hepatic failure (frequency unknown).
  • Renal disorders — blood urea increased.
  • Skin — photosensitivity, rash (common).
    • Rarely: toxic epidermal necrolysis, Stevens–Johnson syndrome, erythema multiforme, exfoliative dermatitis, and fixed eruption.
  • Other rare adverse effects include:
    • Arthralgia, myalgia.
    • Flushing.
    • Severe headache and/or visual disturbances — may be an early symptom of benign intracranial hypertension, a rare but serious adverse effect. Headache is a relatively common side effect.
    • Tinnitus.

 [BNF, 2022; EMC, 2024]

Contraindications and cautions

Do not prescribe doxycycline to:

  • Children under the age of 12 years.
  • Pregnant or breastfeeding women.

Prescribe doxycycline with caution to people with:

  • Alcohol dependence.
  • Renal impairment (avoid excessive doses).

[ABPI, 2016b; BNF, 2022]

Drug interactions

No drug interactions are expected with topical doxycycline.

Lidocaine hydrochloride

Dose

Lidocaine ointment:

  • Adults — apply as required, rub sparingly and gently on affected areas.

Xylocaine® spray:

  • Adults — apply thinly to the ulcer using a cotton bud.

[BNF, 2022]

Adverse effects

Adverse effects of topical lidocaine include:

  • Allergic reactions.
  • Ulceration.
  • Dermatitis.

[ABPI, 2015; BNF, 2022]

Contraindications and cautions

  • Do not prescribe lidocaine to people with:
    • Hypersensitivity to anaesthetics of the amide-type.
    • Porphyria — lidocaine has been shown to be porphyrinogenic in animals.
  • Prescribe lidocaine with caution to people with:
    • Hepatic impairment — due to increased risk of adverse effects.
    • Severe renal impairment — due to increased risk of accumulation of lidocaine and its active metabolite.

[ABPI, 2015; BNF, 2022]

Drug interactions

Drug interactions with lidocaine include:

  • Other local anaesthetics or agents structurally related to amide-type local anaesthetics, for example antiarrhythmic drugs such as mexiletine — toxic effects are additive.
  • Erythromycin and itraconazole — the toxicity of oral lidocaine may be markedly increased.
  • Class III antiarrhythmic drugs (for example amiodarone) — may incur additive cardiac effects in combination with lidocaine.

[BNF, 2022]

Cyanocobalamin

Dose

  • Adults — 50 to 100 micrograms daily, dose to be taken between meals. It should be noted that the BNF considers cyanocobalamin 'less suitable for prescribing'.

[BNF, 2022]

Adverse effects

Adverse effects of cyanocobalamin include:

  • Sensitization which may present as an itching exanthema (rare), and exceptionally, as anaphylactic shock.
  • Acneform and bullous eruptions (rare).

[BNF, 2022]

Contraindications and cautions

Do not prescribe cyanocobalamin to people with hypersensitivity to the product or any of its excipients.

[BNF, 2022]

Drug interactions

Drug interactions with cyanocobalamin include:

  • Para-aminosalicylic acid, colchicine, biguanides, neomycin, cholestyramine, potassium chloride, methyldopa, and cimetidine — reduce the absorption of cyanocobalamin.
  • Chloramphenicol — may attenuate the response to cyanocobalamin.

[ABPI, 2014]

Supporting evidence

This CKS topic is largely based on information contained in the Guideline for diagnosis and treatment of recurrent aphthous stomatitis [Tarakji, 2015] and expert opinion in narrative review articles [Scully, 2016; BMJ Best Practice, 2018; Manfredini, 2021]. Additionally several systematic reviews and meta-analyses informed management options. The recommendations relevant to primary care were developed from the expert opinion of the authors of these reviews, following narrative reviews of the evidence, where available. The evidence for specialist management strategies is not discussed as they are beyond the scope of this CKS 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 aphthous ulcer.

Search dates

July 2017 - February 2022

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 Stomatitis, Aphthous/, aphthous ulcer.tw., mouth ulcer.tw., canker sore.ti,ab,tw., aphthous stomatitis.ti,ab,tw.
  • (Aphthous or Apthous) ulcer.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.
    • Guideline development groups where the topic is an implementation of a guideline.
    • The British National Formulary team.
    • The editorial team that develop MeReC Publications.
  • Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

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

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  • ABPI (2015) SPC for Anbesol adult strength gel. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • ABPI (2016a) SPC for Corsodyl 0.2% mouthwash. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk [Free Full-text]
  • ABPI (2016b) SPC for vibramycin-D dispersible tablets 100mg. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • ABPI (2017) SPC for benzydamine 0.15%w/v oromucosal spray. Electronic Medicines Compendium. Datapharm Communications Ltd.. www.medicines.org.uk/emc/ [Free Full-text]
  • Alli, B.Y., Erinoso, O.A. and Olawuyi, A.B. (2019) Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: a systematic review. Journal of Oral Pathology and Medicine 48(5), 358-364. [Free Full-text]
  • Al-Maweri, S.A., Halboub, E., Al-Sufyani, G., et al. (2019) Is vitamin D deficiency a risk factor for recurrent aphthous stomatitis? A systematic review and meta-analysis. Oral Diseases. [Free Full-text]
  • Al-Maweri, S.A., Halboub, E., Ashraf, S., et al. (2020) Single application of topical doxycycline in management of recurrent aphthous stomatitis: a systematic review and meta-analysis of the available evidence. BMC Oral Health 20(1), 231. [Free Full-text]
  • Al-Maweri, S.A., Halboub, E., Al-Sharani, H.M., et al. (2021) Association between serum zinc levels and recurrent aphthous stomatitis: a meta-analysis with trial sequential analysis. Clinical Oral Investigations 25(2), 407-415. [Free Full-text]
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