Aphthous Ulcers

Overview

This Guidelines summary has been developed to assist community pharmacy teams providing first contact to:

• confirm a diagnosis of aphthous ulcers in primary care
• identify intra- or extra-oral causes of aphthous ulcers, and manage appropriately
• arrange specialist referral where appropriate
• advise on oral hygiene and lifestyle measures to manage aphthous ulcers.

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

Reflecting on Your Learnings

Reflection is important for continuous learning and development, and a critical part of the revalidation process for UK healthcare professionals. Click here to access the Guidelines Reflection Record.

Definition and Prevalence

Definition

• 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.

Prevalence

• Recurrent aphthous ulceration is seen worldwide and may affect up to 25% of the population
• Aphthous ulcers are more common in:
  • women
  • people under 40 years of age
  • non-smokers
  • people of high socioeconomic status.

Causes, Complications, and Prognosis

Possible Causes

• Genetic predisposition—a positive family history can be found in up to 40% of people
• Smoking cessation
• Iron, folic acid, or vitamin B12 deficiency
• Hormonal factors—in some women, ulcers coincide with the luteal phase of the menstrual cycle and may remit with oral contraceptives or during pregnancy
• 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).

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.

Differential Diagnoses

Oral Malignancy

• Suspect oral malignancy 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 is increased with heavy smoking, heavy alcohol drinking, age over 45 years, and male sex. Other forms of tobacco use, and chewing betel, gutkha, or pan, also raise suspicion

For more information, see the NICE CKS topic, Head and neck cancers.

Aphthous-like Ulcers

• Aphthous-like ulcer 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 B 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 than 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.

Other Differential Diagnoses

• 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
• 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 keratinised, particularly palatal, oral mucosa
• Adverse drug reaction (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
• Hand, foot, and mouth disease—blister-like lesions may also be seen on hands or feet
• Periodic syndrome, periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA)—although rare, this tends to occur in young children.

Management

• 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)
    • 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 Society for Oral Medicine and Patient.info
  • 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
    • first-line treatment is usually a topical corticosteroid such as hydrocortisone oromucosal tablets, beclomethasone spray, or betamethasone soluble tablets. Duration of treatment is decided on a case-by-case basis
    • other therapies that can be used either 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
    • 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
  • consider specialist referral if ulceration is severe and does not respond to topical treatments or systemic corticosteroids.

Prescribing Information

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

For information on adverse effects, contraindications and cautions, and drug interactions associated with the following treatments, refer to the full guideline.

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 mcg, twice daily
• For detailed information on the contraindications and cautions, adverse effects, and drug interactions for beclometasone dipropionate, see the NICE CKS topic, Corticosteroids—inhaled.

Betamethasone Soluble Tablets

• Dose for children aged 12 years and over, and adults: 500 mcg, four times a day, to be dissolved in 20 ml water and rinsed around the mouth. Not to be swallowed.

Hydrocortisone Oromucosal Tablets

• Dose for children and adults: one lozenge, four times a day, allowed to dissolve slowly in the mouth in contact with the ulcer.

Oral Prednisolone

For detailed prescribing information on oral prednisolone, see the NICE CKS topic, Corticosteroids—oral.

Benzydamine Hydrochloride

• Mouthwash dose: children aged 13 years and over, and adults—rinse 15 ml every 1.5–3 hours as required. Dilute with an equal volume of water if stinging occurs
• Oromucosal spray dose:
  • children 1 month to 5 years—one spray to the affected area every 1.5–3 hours (maximum per dose, four sprays every 1.5–3 hours), one spray per 4 kg body weight
  • children 6–11 years—four sprays to the affected area every 1.5–3 hours
  • children 12 years and over, and adults—four to eight sprays to the affected area every 1.5–3 hours.

Chlorhexidine

• Mouthwash dose: children and adults—rinse 10 ml twice daily for about 1 minute
• Dental gel dose: children and adults—apply up to twice daily to affected areas
• Oromucosal spray dose: children and adults—apply up to 12 sprays twice daily to affected areas.

Doxycycline Rinses

• Dose for children aged 12 years and older, and adults: 100 mg four times a day. Stir the dispersable tablet into a small amount of water, rinse around the mouth for 2–3 minutes. Preferably do not swallow.

Lidocaine Hydrochloride

• Lidocaine ointment dose: adults—apply as required; rub sparingly and gently on affected areas
• Lidocaine spray dose: adults—apply thinly to the ulcer using a cotton bud.

Cyanocobalamin

• Dose for adults: 50–100 mcg daily; dose to be taken between meals.