Recurrent Aphthous Ulceration

This is the most common ulcerative disease of the oral mucosa and can affect as many as 15-20% of the population at some time in their lives [152]. It is characterised by persistently recurrent, painful oral ulcers [142, 143, 193]. The condition usually starts in early childhood and typically resolves spontaneously in the late teens or early adult life. When the condition develops in older individuals, predisposing causes such as haematinic deficiencies or smoking cessation are more likely to be associated.

There are three main clinical forms of the condition: minor, major and herpetiform ulceration, although a minority of patients may show various combinations of these types. Minor aphthae are by far the most common manifestation (~85%) and are characterised by the formation of one or several superficial ulcers, usually 28 mm in diameter with a yellowish-grey, fibrinous floor and an erythematous halo. The ulcers tend to involve the non-keratinised mucosa such as the lips, buccal mucosa, ventrum of the tongue and floor of the mouth. They usually heal within 7-10 days by regeneration of the epithelium across the floor of the ulcer, and without scarring. The ulcers frequently recur at regular intervals, typically of 2-3 weeks. Some patients, however, are virtually never ulcer free, as new crops appear before pre-existing ones have healed. A minority of cases are menstruation-related and the ulcers appear monthly in the premenstrual week. Major aphthae are less common (~10%) and ulcers can form on both keratinised and non-keratinised mucosae. The ulcers are usually single but can be several centimetres in diameter and are penetrating. Hence, healing is by secondary intention and characterised by granulation tissue formation and scarring. In severe cases the scarring following progressive ulceration can be so severe that it causes trismus and microstomia. Herpetiform aphthae are uncommon

(~5%) and are characterised by the formation of sometimes hundreds of small (~2 mm), superficial ulcers that frequently coalesce and may form on a background of more generalised mucosal erythema [154]. Any oral site may be involved, but the labial and ventral lingual mu-cosae are the sites of predilection.

Although most cases of recurrent aphthous stomatitis are idiopathic, a minority are caused, or exacerbated, by deficiencies in iron, vitamin B12 or folate, and as such are potentially curable. Haematinic deficiencies are reported to be twice as common in patients with recurrent aphthous stomatitis compared with controls. The condition is often made worse by emotional stress. Occasional cases are said to be related to gastro-intestinal complaints such as coeliac disease, Crohn's disease and ulcerative colitis, but some of the data are conflicting [56, 164]. However, it is likely that in most instances any associations are secondary to haematinic deficiencies.

It is uncommon for recurrent aphthae to be biopsied, except when a major aphtha simulates malignancy [97]. Reported early changes include infiltration of the epithelium by lymphocytes and histiocytes and focal aggregates of lymphocytes in the superficial corium. This is followed by areas of epithelial cell apoptosis, degeneration and necrosis [77]. The epithelium is lost and the subsequent ulcer is covered by a fibrinous slough, heavily infiltrated by polymorphonuclear leukocytes. More deeply there is a mononuclear cell infiltration and peri-vascular cuffing is an inconsistent feature. The condition appears to be a T-cell mediated immunological response [62] and is thought to be a response to a kerati-nocyte-associated antigen that is yet to be identified.

more characteristic of Behcet disease, but the significance of this observation is questionable.

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