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AN OVERVIEW of VESICOBULLOUS CONDITIONS AFFECTING the ORAL MUCOSA EMMA HAYES, STEPHEN J CHALLACOMBE Prim Dent J

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AN OVERVIEW of VESICOBULLOUS CONDITIONS AFFECTING the ORAL MUCOSA EMMA HAYES, STEPHEN J CHALLACOMBE Prim Dent J AN OVERVIEW OF VESICOBULLOUS CONDITIONS AFFECTING THE ORAL MUCOSA EMMA HAYES, STEPHEN J CHALLACOMBE Prim Dent J. 2016; 5(1):46-50 in the palate, buccal mucosa and labial ABSTRACT mucosa there is an underlying submucosa. The epithelium is formed of several layers, Vesicobullous diseases are characterised by the presence of vesicles or bullae at the deepest being the layer of progenitor varying locations in the mucosa. The most common occurring in the oral cavity cells forming the stratum germinativum, are mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV). Both adjacent to the lamina propria. are autoimmune diseases with a peak age onset of over 60 years and females Keratinocytes increase in size and flatten are more commonly affected than men. This paper reviews the structure of the as they move through the stratum spinosum oral mucosa, with specific reference to the basement membrane zone, as well and stratum granulosum to the stratum as bullous conditions affecting the mucosa, including PV and pemphigoid, their corneum (in keratinized mucosa) where the aetiology, clinical presentation, and management. desmosomes, which hold the cells together, weaken – therefore allowing normal Learning outcomes desquamation. • Understand the common presentation of vesicobullous diseases. • Appreciate the role of investigations in diagnosis and its interpretation. In addition to desmosomes, epithelial • Appreciate the roles of both primary and secondary care in patient management. cell-cell contact occurs via occludens (tight junctions), and nexus junctions (gap junctions), with each having a complex structure. Desmosomes are small adhesion Introduction proteins (0.2µm) 1 which guarantee the Vesicobullous diseases are characterised by integrity of the epidermis by linking the the presence of vesicles or bullae at varying intermediate filaments within cells to the locations in the mucosa. They often affect plasma membrane as well as adjacent both the skin and oral mucosa, but can on cells, therefore functioning both as an occasion affect only oral mucosae. The adhesive complex and as a cell-surface most common of the vesicobullous diseases, attachment site for the keratin intermediate which occur in the oral cavity are PV and filaments of the cytoskeleton. Desmosomes MMP. Both are antibody-mediated contain a series of proteins; of particular autoimmune diseases but the target interest with regard to bullous diseases antigens of these two diseases are different. are the desmogleins. The oral and skin In MMP, blisters form owing to antibodies epithelium both express desmoglein 3 binding to components of the basement (DSG3) and desmoglein 1 (DSG1) within membrane zone (BMZ) and in PV to desmosomes, but in the oral mucosa DSG3 KEYWORDS molecules on the surface of keratinocytes. is expressed at a much higher level that Bullous, Basement Membrane Zone, The aetiology, pathology, clinical DSG1, 2 which is important in disease Pemphigus Vulgaris, Mucous presentations, and the treatment of these manifestation and antibody detection Membrane Pemphigoid conditions are discussed. It is outside the for diagnosis. 3 scope of this paper to include full details of the infectious causes of bullae, such Between the epithelial cell layers and AUTHORS as those seen in primary herpetic the lamina propria is a complex structure Emma Hayes BDS gingivostomatitis. linking the two layers, known as the BMZ. DCT2 Oral and Maxillofacial Surgery, St George’s The 1-2µm thick 4 BMZ (Figure 1) consists Hospital, London and Department of Oral Medicine, Guy’s and St Thomas’ Hospital NHS The structure of the of the basal cell plasma membrane, the Foundation Trust and King’s College London. oral mucosa lamina lucida, the lamina densa, and the Stephen J Challacombe PhD, The oral mucosa is a specialised stratified sub-lamina densa. On the epithelial surface FDSRCSE, FDSRCS, FRCPath, FMedSci, DSc, FKC squamous epithelium, which is keratinized of the plasma membrane of the basal Department of Oral Medicine, Guys & St Thomas in areas of high friction (dorsal tongue, keratinocytes are small electron-dense Hospitals NHS Foundation Trust and King’s College 5 London Dental Institute, London. palate, and gingiva), with an underlying domains called hemidesmosomes. These connective tissue layer (lamina propria); are specialised, multiprotein complexes 46 PRIMARY DENTAL JOURNAL Figure 1: The basement membrane zone linking epithelial cells to the connective tissue that contribute to the attachment of presentation have a 22% risk of developing epithelial cells to the underlying BMZ. them over five years. 9 Nasal involvement A number of proteins that are implicated may present as bleeding or crusting, in the pathogenesis of subepithelial or laryngeal involvement as hoarseness subepidermal blistering diseases such or dysphagia, and genital involvement as MMP are associated with the as painful erosions. hemidesmosomes (such as BP230 and BP180). 6 The second variant presents with desquamative gingivitis and involves only The lamina lucida consists of laminins the gingivae around the teeth. The gingivae (adhesive glycoproteins which contribute are highly erythematous and hyperaemic to cell adhesion as well as cell migration (Figure 3), and small bullae may be formed and organisation) and is 20–40nm thick. in protected areas around the teeth. This Anchoring filaments transverse the lamina needs to be differentiated from more lucida perpendicularly from the basal cell common causes of desquamative gingivitis membrane to the underlying lamina densa, such as lichen planus. It is distinct from Illustration by BS Bhogal which contains heparin sulphate coated plaque-induced gingivitis in that it extends type IV collagen. beyond the marginal gingivae; as it is antibody-mediated it will not resolve with Mucous Membrane improvements in oral hygiene, and these Pemphigoid patients therefore require referral to Pemphigoid comprises of an uncommon secondary care for diagnosis and heterogeneous group of disorders – management. including MMP and linear IgA disease – characterised by subepithelial separation Diagnosis and deposition of autoantibodies and Diagnosis is confirmed with a biopsy complement along the basement membrane and immunofluorescence. Histologically, zone. MMP is distinguished from skin subepithelial bullae are seen, with no bullous pemphigoid by its predilection acantholytic cells, and the epithelium for mucosal sites and the tendency to form tends to detach itself from the underlying scars, leading to oesophageal strictures, lamina propria. laryngeal stenosis, and blindness in extreme cases of conjunctival cicatrisation. 7 Most cases are detected after the fifth decade, with a mean age of 62, 8 and the disease is more frequent in women than in men. Intraorally two variants of MMP are seen. The most common manifests as bullous lesions or, more commonly, ulceration involving much of the non-keratinized and occasionally the keratinized mucosa; these are subepithelial, may be blood-filled (Figure 2), and last longer (up to several days) than those seen in PV (see Table 1). Irregular erosions or ulcers can be seen after the bullae burst. Bullous lesions can also involve the conjunctiva, nose, larynx, pharynx, oesophagus, genitals, and anus. The oral lesions usually heal without scarring unlike those of the conjunctiva; ophthalmological assessment is therefore important in patients presenting with Figure 2: Irregular oral ulceration in the Figure 3: Desquamative pemphigoid (those without ocular signs at buccal mucosa of a patient with MMP gingivitis in MMP VOL. 5 NO. 1 FEBRUARY 2016 47 AN OVERVIEW OF VESICOBULLOUS CONDITIONS AFFECTING THE ORAL MUCOSA those with both circulating IgA and IgG to Pemphigus vulgaris BMZ are associated with more persistent PV is a potentially lethal, chronic, bullous disease. 12 A further group has circulating disease of the stratified squamous mucosa IgG antibodies that bind to the dermal side and skin, which commonly affects the oral of salt-split skin and recognise laminin 5. mucosa and may initially present orally. More than 90% of patients may have Treatment oral lesions at some stage of the disease. If the disease is confined to the mouth In the UK it occurs mainly in adults with and with a low severity score, topical a median age of 71 at presentation 14 ; corticosteroids are often adequate to it is rarely observed in children and control the lesions. In the more severe adolescents. 15 cases, however, and if there is involvement of other sites, systemic corticosteroids may Clinically, PV can present as painful, be needed. In order to keep the steroid fragile, fluid-filled blisters, which may dose to a minimum and reduce steroid- appear on any areas of the oral mucosa related side effects, such as increased and burst within a few hours; as a result, susceptibility to infections, diabetes, clinical examination often only reveals Figure 4: Intraoral PV showing irregular osteoporosis and hypertension, an shallow ulcers or erosions (Figure 4). ulceration of the dorsum of the tongue immunosuppressant such as azathioprine Clinically there should be little difficulty or dapsone can also be used. MMP is a in differentiating lesions from recurrent chronic disease, which persists, often with aphthous ulcers as they are large and Immunofluorescence (IMF) is a technique exacerbations and remissions, over many erythematous with irregular outlines and which uses fluorescently-labelled years. Disease severity as well as response are persistent ulcers, not recurrent
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