Recurrent aphthous ulceration

Mr Anish Shah outlines the features and treatment of this common oral mucosal condition.

Conditions affecting the immune system may increase the likelihood of recurrent aphthous ulceration
Conditions affecting the immune system may increase the likelihood of recurrent aphthous ulceration

Recurrent aphthous ulceration (RAU, or aphthous stomatitis) is the most common oral mucosal condition. It affects up to a quarter of the population. Women are more affected than men.

RAU can be differentiated from other oral diseases by its tendency to recur, multiplicity and chronicity.

Several factors have been implicated in the aetiology. Deficiency of vitamin B12, folate or iron has been reported in patients with RAU. Treatment of the deficiency may bring a rapid resolution or reduction in the ulcers.

Other conditions to note are sideropenia, neutropenia, leukaemia, myelofibrosis, myelo-dysplasia and multiple myeloma.

GI enteropathy, usually secondary to malabsorption or inflammatory GI disorder, can cause RAU. Examples include Crohn's disease, ulcerative colitis and coeliac disease. Treatment of these conditions may help to reduce the severity and frequency of RAU.

Associated conditions
There are dermatological associations: lichen planus is defined as a mucocutaneous inflammatory condition of unknown aetiology and can be involved in recurrent ulceration of the oral cavity. Other conditions include vesiculobullous diseases such as pemphigus, pemphigoid and linear IgA disease.

In some women, RAU can be associated with the luteal phase of the menstrual cycle.

However, there is little evidence to support the use of hormonal therapy.

Connective tissue diseases such as SLE, Reiter's disease, mixed connective tissue disease and Felty's syndrome may be associated.

There is evidence that a genetic predisposition to RAU exists.

Oral ulceration is a recognised feature of HIV/AIDS. Frequency and severity correlate with the degree of immu- no-deficiency.

A compromised immune system often results in increased frequency of ulcers. Certainly patients undergoing chemotherapy and/or head and neck radiotherapy report several oral complications including ulceration.

RAU occurs almost exclusively in non-smokers. Ulcers often become apparent in patients who have stopped smoking, although the exact mechanism is unclear. RAU as a result of smoking cessation is not usually a persistent problem. Oral cancers must be considered in patients who smoke or have smoked (see box above).

Foods associated with RAU include tomatoes, cinnamon and ingredients such as sodium lauryl sulphate, found in toothpaste. Some patients report RAU associated with stress.

Other potential associations are Wegener's granulomatosis, midline lethal granuloma, Langerhans' cell histiocytosis, hypereosinophilic syndrome or angiolymphoid hyperplasia with eosinophilia.

The usual history involves RAU ulcers recurring at regular intervals (once or twice per month). The ulcers generally last up to 10 days, although occasionally patients report having continuous ulcers, with no 'ulcer free' periods. The peak age of onset is in early adulthood.

Ulcers are broadly divided into three categories. Minor aphthae are the most common. They are shallow ulcers, rounded and approximately 5-7mm in size. There can be one or more and they usually affect non-keratinised mucosa (lateral tongue, buccal mucosae, sulcuses).

Major aphthae are less common. They are often larger than 1cm and can last several weeks. Scarring can follow resolution.

Herpetiform aphthae are usually 1-2mm in size. Many ulcers can be present - up to several hundred in some cases. Ulcers may coalesce to form larger, irregular ulcers.

Several factors are crucial in diagnosing RAU. The most important diagnostic feature is the history. Recurrent ulcers that heal on a regular basis are features of RAU. Behcet's disease is a condition in which the patient can present with a similar pattern of oral ulceration.

Other rare conditions include MAGIC syndrome (mouth and genital ulcers with inflamed cartilage) and PFAPA (periodic fever, aphthous stomatitis, pharyngitis and adenitis).

It is usually the frequency of the ulcers that prompts patients to seek help. Routine haematological investigations are essential and should include tests for ferritin, folate and B12. Any deficiencies should be treated and this usually reduces the frequency of ulceration.

Patients should be educated that the condition can usually be alleviated but may not be cured. A significant proportion resolve spontaneously.2

Hydrocortisone pellets dissolved in the mouth three times a day can give some relief to patients. These can be offered to those patients who suffer from frequent ulcers.

It is thought that they reduce inflammation and so may be used continuously for a couple of months before a reassessment.

Triamcinolone in an adhesive paste is another topical steroid treatment. It can be difficult to apply but is useful for those who suffer with infrequent ulcers.

A relatively new and effective treatment is a steroid asthma inhaler, for example, beclometasone 50-100 micrograms, sprayed twice daily onto the oral mucosa, which can be useful in managing oral ulceration (unlicensed indication).

Betamethasone tablets dissolved in water to make a mouthwash (500 microgram) used three times daily and held in the mouth (not swallowed) for two to three minutes can be useful.

Mouthwashes containing chlorhexidine 0.2% can be beneficial. However, long-term use can lead to parotid swelling and tooth staining.

Major aphthae and/or persistent aphthae (with or without other concurrent underlying systemic disease) may need more aggressive treatment. This may involve systemic steroids, azathioprine, colchicine, dapsone and mycophenolate mofetil. These drugs however should be prescribed under specialist supervision.4

  • Mr Shah is a specialist oral surgeon, Southend Hospital NHS Foundation Trust, Essex

Red flags
Warning signs in recurrent aphthous ulcer

  • An ulcer present for more than three to four weeks
  • An ulcer with a rolled border
  • An ulcer that is indurated
  • An ulcer in high-risk patients, for example, smokers or drinkers
  • Any non-healing ulcer should be urgently referred to an oral surgery/medicine unit

1. Jurge S, Kuffer R, Scully C, Porter S. Mucosal disease, series VI. Recurrent aphthous stomatitis. Oral Dis 2006; 12(1): 1-21.

2. Cawson R, Odell E. Cawson's Essentials of Oral Pathology and Oral Medicine, eighth edition. Churchill Livingstone, 2009. pp221-2.

3. Herlofson B, Barkvoll P. Sodium lauryl sulfate and recurrent aphthous ulcers. Acta Odont Scand 1994; 52(5): 257-9.

4. Scully C, Flint S, Moos K, Porter S. Oral and Maxillofacial Diseases, third edition. Informa Healthcare, 2004.

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