Presentation

Most ulcers which present are painful and therefore present early; the notable exception is that of oral carcinoma in its early stages. A note should be made of the duration of the ulcer, associated local and systemic problems and risk factors (such as travel, smoking and alcohol).

Examination

• Sit opposite the patient and, ideally, wear a headlamp (to keep both hands free).
• Note the patient's facies, looking for lumps, scars and telltale signs of risk factors not offered in history.
• Examine lips, ask the patient to open their mouth (and to remove dentures if present): look at the buccal mucosa, tongue (don't forget to look under the tongue), the gums and the teeth.
• Note lesion location, size and associated features (eg pigmentation, bleeding, presence of plaques or sloughed mucosa).
• Next, look at hard palate (looking for previous trauma, pigmentation and telangiectasia).
• Using a tongue depressor, ask the patient to protrude their tongue and say "aah" in order to assess the oropharynx.
• Palpate a lesion with a gloved finger: tethering or induration is suspicious and warrants further investigation.

Aetiology^[2][3]

These lesions can arise as a result of a number of (sometimes overlapping) disorders outlined in the box and described in more detail below.

Local causes of oral ulceration^[4]

Mechanical trauma

• Essence - this is the most common cause of oral mucosal ulceration.^[2] It may be acute or chronic and is characterised by a shallow base and non-raised margins. Mechanical trauma can occur via a number of mechanisms, from biting the cheek or tongue to the presence of a foreign body. Factitious trauma occurs as a result of deliberate biting or scratching the mucosal surfaces with finger nails.
• Suggestive features - history, ulcer size and location compatible with history and on removal of cause, signs of healing appear within 10 days.

Chemical injury

• Essence - chemical injury can arise from direct contact of oral mucosa with aspirin (leaving white plaques which slough off) or bleach, as may occur when improperly cleaned/rinsed dentures are worn. Recurrent use of phenols or silver nitrate for aphthous ulcers can also give rise to these ulcers.
• Suggestive features - as for mechanical trauma. In the case of bleach associated with dentures, look for a line of ulceration along the gums. Chemical and thermal ulcers tend to be more painful than mechanical ulcers.

Thermal injury

• Essence - ulcers arising from mucosal contact with hot food or liquids.
• Suggestive features - history. The palate is the most commonly affected site but look for associated lip, tongue or oropharyngeal burns.

Recurrent aphthous ulceration^[4][5]

• Synonyms - canker sores, aphthous stomatitis, recurrent aphthous stomatitis (RAS), recurrent oral ulceration (ROU).
• Essence - recurring (days-months) ulcers of unknown exact aetiology (but suggestive risk factors). Characterised by clearly defined, painful, shallow rounded ulcers notassociated with systemic disease. They are not infective. Usually they begin in childhood (most common in young adults: 60% have a suggestive history) and may decrease in frequency/severity with age. They are also more common in women, white people, nonsmokers and people of higher socioeconomic status. They are classified according to size and progression:

  Minor Aphthae	Major Aphthae	Herpetiform Aphthae
  Most common (80% of aphthae). Prodromal tingling 1-2 days. Shallow oval lesions, 2-8 mm diameter. Grey/yellow membrane. Occur in clusters (less than 5). Painful for 4 days or so. Heal completely in 10-14 days without scarring.	Uncommon, 10% of aphthous ulcers. Irregular deep, raised borders 1-3 cm in size. Patients rarely free of ulcers. Extensive residual scarring. Biopsy to rule out squamous cell carcinoma.	Misnomer - not herpetic! Clusters of 5-100 small (less than 3 mm) lesions: may fuse to form larger, painful lesions. Heal completely in 10-14 days.

• Suggestive features - family history (40% positive) and occasionally: local trauma, stress, food sensitivity (chocolate, coffee, peanuts, almonds, strawberries, cheese, tomatoes and wheat flour and some preservatives and flavouring agents), hormonal change (these ulcers tend to subside during pregnancy) and cessation of smoking. Lesions as described above: these tend to be confined to the soft mucosa of the mouth and to non-keratinised mucosa not immediately adherent to the bone; they may be found elsewhere in the digestive tract but they then tend to be associated with other systemic disease.
• Management issues:
  • Try to identify and to minimise any precipitating factor.
  • Offer symptomatic treatment for pain, eg benzydamine hydrochloride.
  • A short course of a low-potency topical corticosteroid (eg triamcinolone in adhesive paste or hydrocortisone lozenges) may benefit some patients.
  • If the pain is so severe that tooth brushing is not possible, add antibacterial mouthwash to prevent secondary bacterial infection.
  • Use of topical corticosteroids in the prodromal phase (tingling/swelling) may be helpful.
  • In some cases, treatment is not needed and reassurance will do; minor aphthae usually present as a mild and self-limiting condition.
  • If ulcers worsen or do not clear over 3 weeks, reassess ± refer for biopsy.

Infective ulcers

• Essence - primary infective causes of chronic oral ulceration are rare - there should be a low threshold for suspecting periodontal disease at least and possible systemic infection or immunodeficiency (see below). Primary herpetic ulceration can occur (most commonly HSV-1);^[2] these lesions are then prone to secondary bacterial infection. Secondary nonspecific bacterial infection of chronic ulcers can delay the healing process. Deep-rooted fungal infection should prompt enquiry as to possible systemic illness. Candida albicans is a normal commensal but it tends to overwhelm other microbes when these are suppressed through long-term systemic antimicrobial treatment or in the immunocompromised. Thus, these patients should be assessed for failure of immunocompetency. HHV-8 is associated with Kaposi's sarcoma of the gingiva.
• Suggestive features - pre-existing oral ulcers, bacterial infection: discharge may be present, fungal infection: depends on the organism but white coating plaques are characteristic of oral candidiasis (thrush). Wearing of dentures can increase the risk of oral candidiasis. Also think of this in the infant who appears hungry but cries every time feeding is attempted. The swollen, ulcerated gingiva of HHV-1 infection may look a little like acute, necrotising, ulcerative gingivitis.
• Management - antiseptic mouthwash.
• Additional notes - in newborns with oral candidiasis, check the child for nappy rash (and possible infection there) and explore the possibility of maternal vaginal candidiasis (source of infection).^[6]

Neoplastic conditions^[4]

• Essence - squamous cell carcinoma (SCC) lesions account for 90% of all oral neoplasia with malignant melanoma, lymphoma and metastases accounting for the remaining 10%. SCC may start as white (leukoplakia) or red (erythroplakia) lesions: white patches carry a 6% risk of malignancy and red lesions are malignant until proven otherwise. Spread occurs via the submandibular and cervical lymph nodes; these will be involved on presentation in 30% of patients. The 5-year survival rate is about 30%.
• Suggestive features - halitosis and a slow-growing painless, nonhealing ulcer with raised borders, usually on the lateral aspect of the tongue, the floor of the mouth or on the soft palate. Tobacco smoking and heavy alcohol consumption strongly increase the risk and act synergistically to increase risk further when combined (100-fold risk in women and 38-fold risk in men).
• Management - refer to a local oral and maxillofacial clinic promptly: primary care management is inappropriate.
• Additional notes - these lesions may mimic lesions of lichen planus, pemphigus or pemphigoid, sialometaplasia or major aphthae.

Irradiation ulcers^[4]

Ulceration occurs either acutely (as a result of direct damage to epithelial cells) or more long-term, secondary to epithelial atrophy and damage to underlying blood vessels. The acute reaction usually begins during the second week of radiation, presenting as erythema followed by spotty mucositis which coalesces to form areas of ulceration covered by a yellow-white pseudomembrane with a bright erythematous border.The lips are often involved. Exquisite pain and burning may be present. Healing generally begins as therapy ends and is usually complete within 3 to 4 weeks, although the discoloration and mucosal atrophy may be lifelong. This often makes dental prosthesis placement difficult. Treatment includes oxidizing mouth rinses.

Ischaemic ulcers: necrotising sialometaplasia^[2]

This is an uncommon disorder that gives rise to large areas of deep ulcers on one side of the hard ± soft palate. This condition is probably associated with an ischaemic event and is associated with factors such as smoking, alcohol use, denture wearing, recent surgery and systemic disease. It can also be a feature of bulimia nervosa. It has been suggested that the local traumas cause ischaemia with resultant tissue necrosis. The clinical and histopathological features may mimic those of SCC.

Systemic causes of oral ulceration

In all these conditions, patients benefit from topical drug treatment for symptom control and may need concurrent antimicrobial treatment for secondary infections. However, ultimately, the underlying cause needs to be addressed.^[7]

Autoimmune conditions

• Behçet's disease:^[4] most of these patients (of Mediterranean, Middle Eastern or Japanese origin) present with some or all of the triad of recurrent aphthous ulcers, eye and genital ulcers. The ulcers can be treated as any oral ulcers but the potential for further systemic involvement warrants careful review ± referral where appropriate.
• Vesicobullous disease: (cicatricial pemphigoid, paraneoplastic pemphigus, pemphigus vulgaris): pemphigus patients may present for the first time with oral ulcers: these are irregular ragged lesions most frequently appearing on the soft palate, buccal mucosa and the gingival mucosa. Pemphigoid patients present with tense blisters which eventually rupture and heal slowly. Steroids are sometimes needed in severe or refractory cases.
• Lichen planus:^[4] look for Wickham's striae (= ring formation of white or violaceous fine, slightly raised thread-like lesions) on the buccal mucosa. They are bilateral, posterior and not seen on the palate. White papules or plaques (and less commonly, erosions and red atrophic areas) may also be found in these areas. A biopsy is often warranted to rule out systemic lupus erythematosus (SLE) and malignancy. Treatment is symptomatic control with topical or systemic steroids. The use of other immunomodulatory agents is often necessary, eg dapsone, azathioprine, ciclosporin and tacrolimus.
• Discoid lupus erythematosus (DLE): 50% of patients affected by mouth ulcers, most commonly found on the cheek (buccal) mucosa.
• Linear IgA disease:^[4] a rare idiopathic condition (sometimes associated with vancomycin and some other drugs, eg diclofenac, penicillin and phenytoin) characterised by linear deposits of IgA molecules in the basement membranes of epithelium. Thus, subepithelial blistering occurs. Treatment involves long-term dapsone - full cure is possible but relapses are also common.
• Other conditions including gluten-sensitive enteropathy, SLE, dermatitis herpetiformis, Wegener's granulomatosis and Kawasaki's disease.

Inflammatory conditions

• Stevens-Johnson syndrome: this is the major form of erythema multiforme. Vesicobullous eruptions tend to occur in young men. The ulcers tend to be diffuse and widespread, although are most commonly seen in the anterior aspect of the mouth. They start off as macules, which develop into blisters which burst to give rise to the ulcer. Oral lesions tend to resolve after six or seven episodes but chlorhexidine mouthwashs help in the interim. Some patients need systemic corticosteroids and/or azathioprine or other immunomodulatory drugs.
• Crohn's disease: persistent solitary ulcers with ragged hyperplastic margins.
• Reiter's syndrome: painless shallow ulcers may appear on the lips, tongue, buccal mucosa and the pharynx.
• Giant cell granuloma.

Drugs

• Cancer agents are widely recognised to disrupt oral mucosa and give rise to an associated stomatitis.^[2] The ulcers tend to appear after the beginning of therapy and peak about a week after the end of therapy.^[4] They gradually subside after this unless a complication such as infection has occurred. They are more likely to become infected due to patient immunocompromise and therefore require concomitant antiseptic mouthwash.
• Other offending drugs include non-steroidal anti-inflammatory drugs (NSAIDs), actinomycin D, gold salts, nicorandil, proguanil, trimetrexate, and zalcitabine. Powdered cocaine and smoking crack cocaine are other causes of mouth ulcers.^[2]

Systemic infection

• Viral infections - Coxsackie A virus, Epstein-Barr virus, hand foot and mouth disease, herpes simplex virus types 1 and 2, varicella zoster virus and as a complication of HIV infection.
• Bacterial infections - tuberculosis, secondary syphilis, Vincent's angina (acute ulcerative gingivitis).
• Fungal infections - candidiasis (see Local causes of oral ulceration, above).
• Other infections - mucocutaneous leishmaniasis.

Inherited conditions

• Autosomal dominant conditions - acatalasia, epidermolysis bullosa (Dowling-Meara type), epidermolysis bullosa simplex.
• Autosomal recessive conditions - epidermolysis bullosa dystrophica, epidermolysis bullosa letalis, junctional epidermolysis bullosa inversa.

Miscellaneous conditions

• Localised oral purpura (angina bullosa haemorrhagica):^[4] these are blood blisters in the mouth, most commonly seen in elderly people, mainly on the soft palate and occasionally on the lateral aspect of the tongue. When the blister bursts, a large round ulcer results. Their origin is not understood but there may be a relation to steroid inhaler therapy. If clotting screen is normal, a biopsy is performed to rule out pemphigoid. This condition spontaneously resolves but topical analgesia is helpful in the interim.
• Haematological disease, notably vitamin B12, folate and iron deficiencies.
• Chronic renal failure.
• Strachan's syndrome.
• Sweet's disease.

Management

General principles

• Establish the cause.
• Symptomatic treatment is local: it aims to protect the area, relieve pain, reduce inflammation and control secondary infection.
• Systemic treatment may be required to address underlying cause.
• An unexplained ulcer of more than three weeks' duration warrants an urgent specialist review.^[3]

Simple mouthwashes

• A warm saline mouthwash (half a teaspoon of salt in a glassful of warm water or dilute compound sodium chloride mouthwash with an equal amount of water) has a mechanical cleansing effect and may relieve the pain of traumatic ulceration.^[4]
• Use until the discomfort and swelling ease.

Antiseptic mouthwashes

• Used in the management of secondary bacterial infection.
• May accelerate the healing of recurrent aphthae.
• Chlorhexidine - this is the mouthwash of choice for aphthous ulcers.^[5] It is also useful in the treatment of denture stomatitis and as prophylaxis in the prevention of oral candidiasis in immunocompromised patients. As a bonus, it inhibits plaque formation. It is available as a mouthwash, gel and spray. It can stain teeth brown if used regularly.
• Hydrogen peroxide - used in the treatment of Vincent's angina: useful for its dual antimicrobial action (good against anaerobes) and mechanical cleansing properties.
• Povidone-iodine - used for the short-term treatment of oral infection (maximum 14 days, owing to iodine absorption).
• Carmellose gelatin paste - this paste adheres to dry mucosa and offers some relief by protecting the ulcer site. It is difficult to apply to some parts of the mouth.

Corticosteroids

• Topical agents are available as oromucosal dissolvable tablets, mouthwashes, pastes and inhaler sprays but mouthwash and spray are unlicensed.
• Use should be limited owing to emergence of candidiasis in the medium- to long-term. (There is little evidence to support the concerns of possible adrenal suppression with these drugs.)^[5]
• Helpful in the prodromal phase of aphthous ulcers and during the active phase, eg hydrocortisone hemisuccinate pellets qds.^[3]
• Triamcinolone in an adhesive paste and hydrocortisone 2.5 mg lozenges are licensed for use in aphthous ulcers.^[5]
• Corticosteroids are contra-indicated in the presence of untreated oral infection.
• There is no role for systemic steroid use in the primary care setting but this may be required under specialist supervision for the treatment of some aphthous ulcers.^[3]
• Oromucosal tablets - hydrocortisone: allow to dissolve next to the ulcer.
• Mouthwash - betamethasone: use regularly (qds) but care is needed to ensure none is swallowed.
• Dental paste - triamcinolone: apply directly to the lesion. It may be difficult to apply.
• Inhaler spray - beclometasone dipropionate: spray twice-daily.

Local analgesics

• These have a limited role as short duration of action precludes good maintenance of analgesia throughout the day.
• They are mainly indicated for intolerable and intractable pain of chronic ulceration (such as with major aphthae).
• Care must be taken not to produce pharyngeal anaesthesia prior to eating (risk of choking).
• Lidocaine - available as 5% ointment/lozenges or 10% solution spray -the latter is applied on a cotton bud which is then held against the ulcer (unlicensed use). Many commercially available preparations contain lidocaine as their active ingredient: check what over-the-counter preparation the patient has already used, prior to prescribing medication.
• Benzydamine hydrochloride - available as mouthwash or spray. Useful in a number of conditions, particularly post-radiation mucositis. If stinging occurs, dilute with an equal amount of water. The spray is helpful to access difficult areas and is licensed for use in children with aphthous ulcers.
• Flurbiprofen - available as lozenges. These NSAIDs can cause mouth ulcers in themselves so they need to be moved around the mouth.
• Salicylates - available as oral gel (massage in up to every 3 hours) or paste (apply with brush 3-4 times a day). Frequent application (especially in children) can lead to salicylate poisoning and these products should not be applied with dentures in situ (allow 30 minutes prior to reinsertion of dentures) as prolonged confinement under a denture may produce ulceration.

Other agents

• Doxycycline mouthwash (mix the contents of a 100 mg capsule with a small amount of water and gargle for 2-3 minutes, repeat qds for 3 days) may be helpful in the management of recurrent aphthous ulceration.
• Low-dose oral doxycycline (eg 20 mg bd for 3 months) is helpful in the management of periodontitis.
• Usual precautions in prescription should be used as with systemic doxycycline use.
• Monitor for emergence of oral candidiasis.