Friday, 6 July 2012

Recurrent aphthous stomatitis (RAS)

Recurrent aphthous stomatitis (RAS) is characterized by recurrent episodes of aphthae [painful ulcers] (Gk, aphtha an eruption in the mouth), each episode lasts from 1 to 4 weeks and the degree of pain varies from mild to extreme. RAS is usually idiopathic and self-limiting. It now seems likely that there is a minor degree of immunological dysregulation underlying aphthae.

RAS is common and affects at least 20% of the population and only in some patients there are identifiable predisposing factors e.g. genetic factors, drug reactions such as nicorandil (nicorandil is a potassium-channel activator with a nitrate component, has both arterial and venous vasodilating properties and is licensed for the prevention and long-term treatment of angina, the mechanism by which nicorandil produces oral ulceration is unclear, there may be a direct local toxic effect of nicorandil on the oral mucosa, nicorandil or a metabolite may be secreted in saliva and similarly produce a toxic effect or alternatively the oral ulcers could be a manifestation of a hypersensitivity reaction to it, the ulcers in such circumstances lack the erythematous halo and the yellow floor typical of aphthous ulcers), deficiencies of iron, folic acid or vitamin B12, HIV infection, Behçet’s syndrome, Sweet’s syndrome, and Crohn’s disease.

RAS may be precipitated by stress, trauma, certain foods, certain toothpastes containing sodium lauryl sulphate (sodium lauryl sulphate is a detergent and wetting agent, and is used in medicated shampoos and in toothpastes, prolonged exposure to it may irritate the skin or mucous membranes), menstruation (hormone therapy may be required) and cessation of smoking.

There are three main clinical types of RAS.

Minor aphthous ulcers (80% of all RAS): These are the commonest type.  They occur mainly in the 10 to 40-year age group, and often cause minimal symptoms. Only a few ulcers (one to six) appear at a time; they heal within 14 days and recur at variable intervals. They become less frequent with age. They are  < 10 mm in diameter. The buccal sulcus is a common site. The ulcer floor is initially yellowish but becomes greyish as epithelialisation proceeds. There is an erythematous halo and some oedema but the ulcers heal with little or no evidence of scarring.

Major aphthous ulcers (10% of all RAS): These are larger, recur more frequently, last longer and are more painful than the minor aphthous ulcers.  They appear on any area of the oral mucosa. They are ≥ 10 mm in diameter with considerable pain and they may heal with scarring (in about 60%).

Herpetiform ulcers (10% of all RAS): They tend to occur in patients in their 3rd decade and there is a female predominance. They are often extremely painful. They heal within 14 days but the ulceration may be virtually continuous. They appear on any area of the oral mucosa. Ventrum of tongue is a common site. They begin with vesiculation, which passes rapidly into multiple (up to 100), minute, discrete ulcers. The ulcers increase in size and coalesce to leave large ragged ulcers and they may heal with scarring (in about 30%). Their similarity to herpetic stomatitis gives herpetiform ulcers their name, but there is no evidence that herpes simplex virus is involved.

RAS in most patients resolves or abates spontaneously with age. An underlying, identifiable predisposing factor is particularly likely where RAS commences or worsens in adult life.

Always palpate solitary long-standing non-healing ulcers to check for the induration and if indurated consider biopsy to exclude or confirm oral cancer.

Predisposing and precipitating factors should be corrected when possible.  Good oral hygiene should be maintained.  Use of chlorhexidine mouthwash is often beneficial and may accelerate healing of recurrent aphthous ulcers.

Topical corticosteroid therapy may be used for aphthous ulcers and it is most effective if applied in the ‘prodromal’ phase. Thrush or other types of candidiasis are recognised complications of corticosteroid treatment. Systemic corticosteroid (e.g. prednisolone) may be required at times.

The main indication for a topical local analgesic (e.g. lidocaine 5% ointment or lidocaine 10% spray) is to relieve the pain of otherwise intractable oral ulceration. When local anaesthetics are used in the mouth care must be taken not to produce anaesthesia of the pharynx before meals as this might lead to choking. Choline salicylate dental gel has some analgesic action and may provide relief for recurrent aphthae (for patients > 16 years of age), but excessive application or confinement under a denture irritates the mucosa and can itself cause ulceration.
Doxycycline rinsed in the mouth may be of value for recurrent aphthous ulceration. A 100 mg doxycycline dispersible tablet can be stirred into a small amount of water then rinsed around the mouth for 2–3 minutes 4 times daily usually for 3 days; it should preferably not be swallowed.  Doxycycline stains teeth, avoid in patients < 12 years of age. Oral low-dose tetracyclines may be required at times.
Rebamipide, an amino acid derivative of 2(1H)-quinolinone, is stated to possess cytoprotective properties and has been shown to be effective in treating RAS (course up to 2 weeks) and Behçet's syndrome (longer course). The usual oral dose is 100 mg three times daily.

Buccal bio-adhesive tablet containing amlexanox can also be used for patients ≥ 12 years of age. It is actually a 2-mg biodegradable oral disc designed to deliver amlexanox. It can be used four times daily after meals and before bed. Up to three bio-adhesive tablets may be used at one time. Contact dermatitis reactions have been described with amlexanox so hands must be washed immediately after applying amlexanox directly to the ulcers with the fingertips. Amlexanox has a stabilising action on mast cells resembling that of sodium cromoglicate and also acts as a leukotriene inhibitor. It is used here as an anti-inflammatory preparation.  

Calcineurin inhibitors e.g topical tacrolimus may be effective.

There are multiple, other therapies available for RAS. Colchicine and pentoxifylline for example, may have a role in individual cases but are not generally very effective or have adverse effects. Thalidomide, in doses from 50 mg up to 300 mg daily, can frequently induce remission, especially in major aphthae, but its important teratogenic effects and the risk of neuropathy must be considered. Other examples include dapsone, sodium cromoglicate, and levamisole.

This page was last updated in April 2014.  

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Main Works of Reference List (The first eight are my top favourites)

  • British National Formulary
  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
  • Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health
  • Oxford Handbook of Medical Dermatology
  • Rook's Textbook of Dermatology
  • Simple Skin Surgery
  • Weedon's Skin Pathology
  • A Concise Atlas of Dermatopathology (P Mckee)
  • Andrews' Diseases of the Skin
  • Andrology (Nieschlag E FRCP, Behre M and Nieschlag S)
  • Bailey and Love's Short Practice of Surgery
  • Davidson's Essentials of Medicine
  • Davidson's Principles and Practice of Medicine
  • Fitzpatrick's Colour Atlas and Synopsis of Clinical Dermatology (Klaus Wolff FRCP and Richard Allen Johnson)
  • Fitzpatrick’s Dermatology in General Medicine
  • Ganong's Review of Medical Physiology
  • Gray's Anatomy
  • Hamilton Bailey's Demonstrations of Physical Signs in Clinical Surgery
  • Hutchison's Clinical Methods
  • Lever's Histopathology of the Skin
  • Lever's Histopathology of the Skin (Atlas and Synopsis)
  • Macleod's Clinical Examination
  • Martindale: The Complete Drug Reference
  • Oxford Handbook of Clinical Examination and Practical Skills
  • Oxford Textbook of Medicine
  • Practical Dermatopathology (R Rapini)
  • Sexually Transmitted Diseases (Holmes K et al)
  • Statistics in Clinical Practice (D Coggon FRCP)
  • Stockley's Drug Interactions
  • Treatment of Skin Disease: Comprehensive Therapeutic Strategies
  • Yen & Jaffe's Reproductive Endocrinology