Introduction

An ulcer is defined as a break in the skin or mucous membrane which fails to heal leading to a loss of surface tissue, disintegration and epithelial necrosis.1

Oral ulceration can be idiopathic, infectious, autoimmune or malignant in aetiology. Diagnosis of oral ulceration remains a challenge for clinicians due to the overlap in clinical presentation.2

This article provides a brief overview of the common causes of oral ulceration.


History and examination

History

Along with a comprehensive medical, social, dental and family history, key points to cover in the history include:

  • Number of ulcers present in the oral cavity
  • Duration of ulcer(s)
  • Previous episodes of oral ulceration/frequency of ulceration
  • Any recent changes in medication
  • Associated symptoms such as fever or malaise
  • Any extra-oral changes which may be indicative of an autoimmune disorder

Clinical examination

Important points to address in the clinical examination include:

  • Number of ulcers present
  • Site of the ulceration: on keratinised or non-keratinised mucosa
  • Appearance, margins and base of ulcer(s)
  • Texture of ulcer(s)
  • Mucosal scarring

Recurrent aphthous ulcers

Recurrent aphthous stomatitis (RAS)

RAS is a common oral disorder affecting up to 25% of the population.3

It can be idiopathic or due to an underlying systemic condition.

Aetiology of RAS

The aetiology of RAS remains unknown however a number of factors, including stress, trauma, smoking cessation, hormonal imbalance, food hypersensitivity and genetics can predispose an individual to RAS.4

Clinical presentation

RAS has three typical clinical presentations which are discussed below.

Minor RAS

Minor RAS is the most common clinical presentation. Ulcers appear in clusters of 1-6 on non-keratinised mucosa. Minor RAS is self-limiting and usually heals within 7-10 days with no scarring.

Minor RAS presents clinically as ulcers 2-4mm in diameter with an erythematous margin and yellowish floor (figure 1).4

Major RAS

Major RAS can present on keratinised and non-keratinised oral mucosa. These ulcers are usually greater than 10mm in diameter, occurring in groups of 1-6 (figure 2). Major RAS is self-limiting but can last for several months. These ulcers usually heal with scarring. It is important for clinicians to be aware that these ulcers can mimic a malignant ulcer.4

Herpetiform RAS

Herpetiform RAS is extremely painful. Lesions present as multiple small vesicles usually less than 5mm in diameter coalesce together to form large widespread erythematous areas (figure 3). They usually appear on non-keratinised mucosa, lasting 10-14 days.4

Nutritional deficiencies

Several nutritional deficiencies are linked with the oral manifestation of RAS. The common nutritional deficiencies seen in patients with RAS are iron, vitamin B12 and folate.

It is therefore important to screen for underlying haematinic deficiencies. Investigations to consider include a full blood count (FBC), serum ferritin, serum B12 and folate.

Behcet’s disease

This is a multisystem inflammatory disorder, which commonly presents in the oral cavity as aphthous ulceration. Other defining features of Bechet’s disease include genital ulceration, uveitis, erythema nodosum, arthritis, gastrointestinal lesions, vascular lesions and central nervous system involvement.8

Aetiology

The aetiology Bechet’s is unknown, but a combination of genetic and environmental factors plays a role, affecting all age groups. The HLA-B51 gene is found in the majority of the patients with this disease.8

Clinical presentation

Bechet’s disease presents in the oral cavity as minor, major or herpetiform recurrent aphthous ulceration, recurring at least three times over a 1- year period. Oral ulceration is the hallmark of this disease.8

Crohn’s disease

Crohn’s disease is an autoimmune disorder affecting the gastrointestinal tract.

Aetiology

The aetiology of Crohn’s disease is unknown, however, genetic and environmental factors can predispose an individual to Crohn’s.

Clinical presentation

Approximately 80% of the individuals with Crohn’s disease exhibit oral lesions. These include persistent lip swelling, cobblestone appearance of the oral mucosa, mucogingivitis, deep linear ulceration, aphthous ulcers along with angular cheilitis and perioral dermatitis.9

Ulcerative colitis and coeliac disease

Ulcerative colitis is characterised by a diffuse inflammation of the colonic mucosa, whilst coeliac disease is caused by an abnormal immune reaction to gluten.10

In both, an oral manifestation of RAS is common.


Acute solitary ulcers

Traumatic ulceration

Aetiology

Traumatic ulcers are usually caused by physical, thermal or chemical trauma resulting in damage to the oral mucosa.

These ulcers usually heal within 7-10 days after the cause has been eliminated.

Clinical presentation

The most common sites are buccal mucosa, tongue and lower lip.

Traumatic ulcers usually present as a raised lesion with an erythematous border and yellowish-white necrotic pseudomembrane (figure 4).11

Appearance of a traumatic ulcer on buccal mucosa
Figure 4. The appearance of a traumatic ulcer on buccal mucosa.12

Acute multiple ulcers

Primary herpetic gingivostomatitis

Aetiology

Primary herpetic gingivostomatitis is a common oral manifestation of systemic herpes simplex virus (HSV) infection.11

Clinical presentation

These ulcers can present on keratinised and non-keratinised mucosa.

Typical clinical features of primary herpetic gingivostomatitis include:11

  • Pyrexia
  • Malaise
  • Lymphadenopathy
  • Halitosis
  • Difficulty swallowing
  • Intraoral pinhead vesicles which coalesce into large painful ulcers

Hand-foot mouth disease

Aetiology

This is a highly infectious viral disease caused by the Coxsackie virus affecting infants and children under 5 years of age.13

Site of ulceration

  • Hands
  • Feet
  • Oral cavity: tongue, palate, buccal mucosa, gums, lips

Clinical presentation

Intra-oral lesions present as vesicles which ulcerate resulting in erythematous halos or macules approximately 2mm in diameter.13

Erythema multiforme

Erythema multiforme (EM) is an immunological vesiculobullous disorder affecting the skin and mucous membranes.

It is further categorised into:14

  • EM major: has the involvement of one or several mucous membranes.
  • EM minor: has no mucosal membrane involvement.

Aetiology

The aetiology of erythema multiforme is obscure. Infectious agents such as herpes simplex virus or use of certain drugs (nonsteroidal anti-inflammatories, antibiotics and anticonvulsants) can precipitate erythema multiforme.14

Clinical presentation

EM lesions are acute with mild or no prodromal symptoms. Oral lesions occur on the lips and anterior oral mucosa. The lesions present as asymmetrical, erythematous, lesions. These lesions usually heal without scarring.14


Chronic solitary ulcers

Ulcerative squamous cell carcinoma (SCC)

Ulcerative squamous cell carcinoma often presents as a single persistent ulcer. It is usually asymptomatic in the initial stages.11

Risk factors

Smoking, tobacco chewing and excessive alcohol intake increase the risk of developing oral cancer.

Clinical presentation

These ulcers can present anywhere on the oral mucosa but the following areas are the high-risk sites, where SCC is more likely to develop:

  • The floor of the mouth
  • Lateral and ventral borders of the tongue
  • Retromolar region
  • Lips

An ulcerative SCC can present as a crater-like lesion with rolled out margins, an indurated border and a velvety base (figure 5).11

Figure 5. Ulcerative squamous cell carcinoma of the tongue.15

Chronic multiple ulcers

Pemphigus vulgaris

Pemphigus vulgaris is an autoimmune, life-threatening disease presenting as blisters and erosions of the skin and mucous membrane.13

Clinical presentation

In the oral cavity, the most affected sites are the buccal mucosa, palate and gingivae.

The clinical presentation of the oral lesions starts as a bulla, which breaks to form shallow ulcers. When rubbed, the thin layer of epithelium sheds leaving a denuded base (known as Nikolsky’s sign).13

Mucous membrane pemphigoid

Mucous membrane pemphigoid is an autoimmune blistering disease that affects the basement membrane. This disease can affect the eyes, oral cavity, nasopharynx, larynx, oesophagus, genitourinary tract and anus.13

Clinical presentation

This disease manifests orally as vesicles, erosions, and desquamative gingivitis.


General management of oral ulceration

Primary care management

Along with reassurance and advice, management in primary care may include:

  • Removing the source of trauma: patient education, smoothening sharp teeth/restoration.
  • Chlorhexidine mouthwash.
  • Topical corticosteroids.
  • Topical anaesthetic for symptomatic relief.
  • Regular monitoring of the oral mucosa.
  • Appropriate referral to secondary care.

A 2-week urgent referral to secondary care is required if malignancy is suspected. For all other oral ulcerations where malignancy is not suspected, referrals can be made as urgent or routine to establish a definitive diagnosis or for management, if the condition cannot be managed in primary care.

Investigations

Further investigations are required when the aetiology of oral ulceration is unclear.

Laboratory investigations

Laboratory investigations should aim to exclude underlying nutritional deficiencies and gastrointestinal tract pathology:

  • Full blood count
  • Serum B12
  • Ferritin
  • Folate

Other investigations

  • Biopsy: indicated if there is a clinical suspicion of malignancy or a definitive diagnosis cannot be established clinically.
  • Direct/indirect immunofluorescence: used to help diagnose autoimmune blistering diseases (e.g. pemphigus vulgaris or mucous membrane pemphigoid and connective tissue disorders such as lupus).

These investigations are performed in secondary care.

Secondary care management

Management will differ depending on the underlying condition but may include:

  • Topical or systemic corticosteroids
  • Surgical removal of persistent ulcer
  • Monitoring of oral mucosa.

Reviewer

Dr Rajinder Dodd

OMFS Specialty doctor at Pinderfields General Hospital


Editor

Dr Chris Jefferies


References

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  3. Scully, C. and Shotts, R. Mouth ulcers and other causes of orofacial soreness and pain. Published in 2001. Available from: [LINK]
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  8. Nair, J.R. and Moots, R.J. (2017). Behcet’s disease. Published in 2017. Available from: [LINK]
  9. Lankarani, K.B., Sivandzadeh, G.R. and Hassanpour, S. (2013). Oral manifestation in inflammatory bowel disease: A review. Published in 2013 Available from: [LINK]
  10. Collins, P. and Rhodes, J. (2006). Ulcerative colitis: diagnosis and management. Published in 2006. Available from: [LINK]
  11. Mortazavi, H., Safi, Y., Baharvand, M. and Rahmani, S. (2016). Diagnostic Features of Common Oral Ulcerative Lesions: An Updated Decision Tree. Published in 2016 Available from: [LINK]
  12. Mortazavi, H., Safi, Y., Baharvand, M. and Rahmani, S. Traumatic ulcer coated with pseudomembrane and surrounded by inflammatory halo. License: [CC-BY]. Available from: [LINK]
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