Pathology of the Head and Neck

Oral Cavity Chapter 3 77are present in other than trace amounts mucous membranepemphigoid is a much more likely diagnosis.Linear IgA disease tends to be refractory to systemicsteroids, but it may respond to dapsone or sulphonomides.3.2.11 Erythema MultiformeErythema multiforme is a mucocutaneous inflammatorydisorder, but sometimes the mouth is the only siteof involvement [1, 8]. It can be relatively mild or manifestwith fever, malaise and extensive skin, mucosaland ocular lesions when it is sometimes called StevensJohnson syndrome or erythema multiforme major. Itis thought to be an immunologically mediated disorder,but in many cases no precipitating factor is found.Triggering agents that have been implicated include infectionswith Herpes simplex virus [7] and Mycoplasmapneumoniae [99] and a wide range of drugs includingsulphonamides, anticonvulsants, non-steroidal antiinflammatorymedications and antibiotics. Althoughpatients may suffer a single episode, it is often recurrent.Erythema multiforme is usually seen in young adults(20–40 years) and is more common in males. Oral lesionsmay be the only feature of the disease or cutaneousinvolvement may follow several attacks of oral ulceration.The lips are the most frequently involved siteand typically show swelling and extensive haemorrhagiccrusting. Within the mouth there are usually diffuseerythematous areas and superficial ulcers on the buccalmucosa, floor of the mouth, tongue, soft palate andfauces. It is uncommon for the gingiva to be involvedand this sometimes helps to distinguish erythema multiformefrom primary herpetic gingivostomatitis, wheregingival inflammation is a conspicuous feature. The areasof mucosa involved frequently break down to formpainful, shallow, irregular ulcers on a background ofmore generalised erythema. It is unusual to see intactblisters in the mouth.The classical cutaneous manifestation of erythemamultiforme is the development of so-called target orbull’s eye lesions. These begin as dark red macules, usually1–3 cm in diameter. They become slightly elevatedand develop a characteristic bluish centre. These lesionsare seen most frequently on the hands and lower limbs.In erythema multiforme major there may be ocular andgenital involvement together with constitutional symptoms.A very severe and potentially lethal variant is toxicepidermal necrolysis, when there is widespread cutaneousand mucosal involvement with extensive blisteringand epidermal loss leading to fluid and electrolyte lossand secondary infection.Microscopy shows variable features and early epithelialbreakdown of oral lesions frequently masks anycharacteristic features [25]. In the early lesions there isapoptosis and necrosis of keratinocytes, intercellular oedemaand inflammatory infiltration of the epithelium.This leads to intra- and sub-epithelial vesiculation andultimately loss of the roof of the blister to form an ulcer.There is lymphohistiocytic and polymorphonuclear infiltrationof the superficial corium and the inflammatoryinfiltrate can extend more deeply, often in a perivasculardistribution. Patchy deposits of C3 and IgM maybe found in the walls of blood vessels, but there is nofrank vasculitis and the immune complex depositionappears to be non-specific.3.3 Ulcerative Lesions3.3.1 Aphthous Stomatitis(Recurrent Aphthous Ulceration)This is the most common ulcerative disease of the oralmucosa and can affect as many as 15–20% of the populationat some time in their lives [152]. It is characterisedby persistently recurrent, painful oral ulcers [142, 143,193]. The condition usually starts in early childhoodand typically resolves spontaneously in the late teens orearly adult life. When the condition develops in olderindividuals, predisposing causes such as haematinicdeficiencies or smoking cessation are more likely to beassociated.There are three main clinical forms of the condition:minor, major and herpetiform ulceration, although aminority of patients may show various combinations ofthese types. Minor aphthae are by far the most commonmanifestation (~85%) and are characterised by the formationof one or several superficial ulcers, usually 2–8 mm in diameter with a yellowish-grey, fibrinous floorand an erythematous halo. The ulcers tend to involvethe 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 ofthe epithelium across the floor of the ulcer, and withoutscarring. The ulcers frequently recur at regular intervals,typically of 2–3 weeks. Some patients, however,are virtually never ulcer free, as new crops appear beforepre-existing ones have healed. A minority of casesare menstruation-related and the ulcers appear monthlyin the premenstrual week. Major aphthae are less common(~10%) and ulcers can form on both keratinisedand non-keratinised mucosae. The ulcers are usuallysingle but can be several centimetres in diameter andare penetrating. Hence, healing is by secondary intentionand characterised by granulation tissue formationand scarring. In severe cases the scarring following progressiveulceration can be so severe that it causes trismusand microstomia. Herpetiform aphthae are uncommon