The information - Aphthous ulcers

The patient’s unmet needs (PUNs)

A 22-year-old man attends the surgery complaining of painful mouth ulcers. He has suffered with this problem intermittently for years but this latest crop is proving more painful and longer lasting than usual. ‘I’ve tried all sorts of lozenges and gels from the pharmacist,’ he says, ‘but nothing helps – can you prescribe me something to get rid of them? Am I stuck with these attacks forever?’ He is not on medication, has no significant medical history and is otherwise well, but comments: ‘I searched ‘‘mouth ulcers’’ online and found they can be linked to coeliac disease – should I be tested?’

The doctor’s educational needs (DENs)

How common are aphthous ulcers? What causes them? What is the prognosis?

Recurrent aphthous stomatitis (RAS) is a condition in which the patient experiences recurring bouts of one or more mouth ulcers at varying intervals, causing significant pain when eating, swallowing and speaking.

There are three main types:

Minor RAS

• Ulcers are usually oval and have a yellow/grey base with a thin erythematous border.

• Ulcers may be up to 10mm in diameter.

• Individual ulcers take between three and 14 days to heal.

• In severe cases there may be no ulcer-free period but patients are usually free of ulcers for three to four weeks between attacks. The ulcers heal without scarring. See image, below.

Minor aphthae on the tongue

Major RAS

• Ulcers are usually fewer in number and larger than in minor RAS.

• They take longer to heal (up to months in some cases) and often heal with a scar.

• Any area of the oral mucosa may be affected.

• Peak age of onset is in the first and second decades.

• This type of ulcer is most likely to be mistaken for a malignant ulcer. See image, below.

Major aphthous ulcer on the soft palate

Herpetiform ulcers

• So called because of their resemblance to the vesicles found in primary herpes simplex virus (HSV) infections, though there is no recognised link between herpetiform ulcers and herpes infection.

• The ulcers are small (1-2mm), round and yellow with surrounding erythema.

• The lateral margins of the tongue and floor of mouth are affected and each crop may take seven to 14 days to heal, with varying ulcer-free periods.

• Where ulcers coalesce to form a larger ulcer, the area may heal with scarring.

Herpetiform aphthous ulcers on the palate/soft palate withmarked surrounding erythema

In many cases, no cause for the ulcer is found. Stress, hormone imbalances, certain foods (such as chocolate, cheese and tomatoes), sodium-lauryl sulphate in toothpaste and trauma have been reported as precipitating factors but the evidence is inconclusive. Smoking cessation has been found to be associated with the onset of RAS. Up to 40% of patients report a family history of recurrent mouth ulcers, suggesting a genetic predisposition.¹

What other oral or skin disease may mimic recurrent aphthous ulcers and how may these be differentiated?

Oral/skin disease	Ulcer characteristics	Notes
Oral cancer	Painless with rolled margins, firm on palpation
Drug-induced oral ulceration (nicorandil, NSAIDs, beta-blockers all implicated)	Solitary, oval in shape, present on the lateral border of the tongue Significant inflammatory halo	Healing observed on cessation of the drug
Traumatic ulceration	Single or multiple, may be symmetrical or irregular in shape Chronic, traumatic ulcers (e.g. caused by ill-fitting dentures) may have raised borders
Oral lichen planus	Red or white patches, may have a ‘lace-like’ appearance Mouth ulcers may be surrounded by a ‘lace-like’ pattern of whitening	Spicy and citrus foods often exacerbate symptoms Biopsy is advisable to confirm diagnosis
Pemphigus	Widespread areas of painful ulceration	Generally affects people aged 40-60 years.
Pemphigoid	Ulcerated or red areas that may heal with scarring	Mainly affects those aged over 70 years.
Viral infections (primary herpetic gingivostomatitis, herpangina etc.)	Single episode of ulceration preceded by vesicle formation	Any area of the mouth may be affected.
Erythema multiforme	Variation in appearance – ranging from diffuse oral erythema to multifocal superificial ulcerations	Haemorrhagic crusting of the lips is classic in erythema multiforme Target lesions may be seen on the skin

What conditions are aphthous ulcers associated with? How strong are these links?

Gastrointestinal disease

Approximately 5% of patients with recurrent oral ulcers have coeliac disease. Aphthous ulcers have been found in 22-41% of coeliac patients compared to 7-27% of controls.

Up to a third of patients with Crohn’s disease have changes in their oral mucosa and a significant number complain of oral ulceration. This can be ‘aphthous-like’, but more commonly presents as linear ulceration on the inside of the cheeks, deep in the sulcus, next to the gums and teeth.

Ulcers associated with inflammatory bowel disease may also be due to malabsorption resulting in folic acid, iron, zinc or vitamin B12 deficiencies.²

Nutritional deficiencies

More than 50% of patients with symptoms of RAS have been found to have haematinic deficiencies, compared with 7% of controls. These aphthous ulcers improve with replacement therapy in some cases.

Behçet’s disease

Behçet’s disease is a multisystem, inflammatory disorder characterised by recurrent oral ulcers, genital ulcers, uveitis and skin lesions. To make
a diagnosis, aphthous ulcers (major, minor or herpetiform) should be present along with two of the other signs described.

HIV

Approximately 4% of adults and 5-7% of children with HIV/AIDS will have aphthous ulcers, which can cause considerable debilitation. They are more likely to be of the atypical, major or herptiform-type than in patients with classical RAS and often take longer to heal.

What evidence-based treatments are available, either prescribed or over the counter?

All patients should be recommended to use an analgesic mouthwash and an antiseptic mouthwash. Benzydamine hydrochloride 0.15% and chlorhexidine digluconate (alcohol-free) 0.2% are both available OTC, which will give temporary pain relief, prevent secondary infection and promote healing.

Covering agents and gels that promote healing can also be helpful – for instance Orabase protective paste and Gengigel gel/mouthwash.³ These are not listed in the BNF but are available for patients to buy and can be prescribed by GPs.

Topical steroids – for instance betamethasone sodium phosphate dissolved in water – can be prescribed if symptoms are not readily controlled by OTC remedies.

Other steroid preparations are available, such as soluble prednisolone tablets and fluticasone propionate nasal drops. These topical preparations should be used as soon as the oral ulcers start and should not be swallowed.

For localised areas of ulceration, a steroid spray may be used by directing the spray at the area of ulceration. Alternatively, a hydrocortisone oromucosal tablet can be allowed to dissolve next to an ulcer, up to four times daily. All patients using topical steroids should be monitored for oral candidiasis.

Patients with the herpetiform type of aphthous ulceration may respond to antibiotic mouthwashes.³

Patients for whom topical therapy is ineffective may be offered systemic therapy. These patients should be managed in secondary care with specialist supervision and monitoring for possible side-effects.

Which investigations should the GP arrange? Is a coeliac screen warranted even in the absence of other suggestive symptoms?

In patients with a history of recurrent oral ulceration, you should check:

• FBC.

• Serum vitamin B-12, folate, and ferritin.

• Serology for coeliac disease – anti-tissue transglutaminase (anti-TTG)/anti-endomysial antibody (anti-EMA). This is indicated even in the absence of other GI symptoms as the oral ulcers are occasionally the presenting feature.

Professor Anne Field is an honorary consultant in oral medicine, and Dr Caroline McCarthy is an academic clinical fellow and specialist trainee in oral medicine at Liverpool University Dental Hospital

References