Oral autoimmune vesicobullous diseases: Classification, clinical presentations, molecular mechanisms, diagnostic algorithms, and management

Abstract

Vesicobullous diseases are a large group of disorders with different etiologies, pathogenesis, and prognoses that affect the skin, the mucosal surfaces, or both. The clinical sign that marks all vesicobullous diseases is the onset of vesicles or bullae, defined as skin/mucosal lesions with a subcorneal or suprabasal intraepithelial detachment within the epithelium (acantholysis) or with a subepithelial detachment between the epithelium and the lamina propria. Clinical and histologic findings vary markedly among vesicobullous diseases, depending on the heterogenity of the etiology (Table 1). Many of these diseases can be extremely debilitating with serious sequelae, and are possibly fatal, so early treatment is necessary to reduce morbidity and mortality.In this review we discuss autoimmune blistering disorders, and among them, those that more frequently affect the oral mucosa.Autoimmune blistering disorders are a rare subgroup of diseases that are characterized by the presence of serum autoantibodies (IgG, IgM, IgA) directed against antigens within the epithelium or the basal membrane zone. The different topography of the numerous antigens in the context of the epithelium and basal membrane zone explains the presence of intraepithelial or subepithelial bullous lesions, and identifies different diseases with totally different treatment strategies and prognoses. The application of immuno-molecular biology to the study of autoimmune blistering disorders has led to a more detailed understanding of the pathogenesis of the disorders. The oral mucosa often represents the first site of onset of autoimmune blistering disorders from which the disease may spread to the skin and/ or other mucosal sites (conjunctiva, nose, pharynx, larynx, esophagus, genital area). Oral mucosal involvement is the sole presentation in some cases. For this reason, early diagnosis of autoimmune blistering disorders in oral mucosa is imperative for clinicians to maximize treatment response, minimize serious side effects and, above all, to achieve a good prognosis and better quality of life for the patient. | PEMPHI G US V ULG ARISPemphigus is a group of potentially life-threatening autoimmune blistering diseases characterized by cutaneous and/or mucosal blistering caused by the presence of circulating IgGs directed against desmogleins 1 and 3, calcium-dependent adhesion molecules (cadherins) that are involved in cell-cell adhesion 1 (Figure 1). The interaction between desmoglein IgGs and their target antigens is responsible for acantholysis and the formation of intraepithelial blisters of the skin and mucous membranes. Differences in the location of particular desmogleins (only skin, only mucosal surfaces, skin and mucosal surfaces together) result in different phenotype of the disease. 3 The mean age of onset of pemphigus vulgaris is usually 40-60 years. The disease susceptibility is strongly associated with some class II HLA antigens.The worldwide epidemiology of pemphigus has shown an incidence of 0.1-3.2/100 000 population. 4 The incidence of...

Oral Medicine Considerations for Older Patients

“…19 blisters can present on any part of the oral mucosa but frequently develop in areas subjected to frictional forces. 20 Due to the fragile nature of the blisters, areas of shallow, widespread painful erosions that can persist for months are frequently noted on examination ( Figure 8). Due to the serious and potentially fatal nature of pV, it is imperative that it is diagnosed early and treated with appropriate immunosuppression therapy.…”

Clinical Analysis of Desquamative Gingivitis Related Oral Mucocutaneous Diseases

“…24 However, a definitive diagnosis may be possible only with microscopic examination. 2,[4][5][6] Once a definitive diagnosis of the cause of DG has been established, special multidisciplinary coordinated approaches should be taken because; MMP can affect conjunctiva which may result in subconjunctival scarring (symblepharon) and eventually permanent blindness 22,25 , PV is a serious mucocutaneous disease which can be fatal if untreated, 20,26 and OLP has a risk for malignant transformation. 18 The main limitation of this study was the limited sample size and relatively short observation period.…”

“…3 A careful medical history and intraoral examination for erythematous gingiva and other oral lesions with specific appearances are extremely important in establishing a clinical diagnosis. 2,4 However, DG-related mucocutaneous diseases frequently share similar clinical manifestations, so, further diagnostic methods, based on biopsy for histopathologic and direct immunofluorescence analysis (DIF), are considered to be the gold standard in diagnosis. 1,5,6 Previous studies demonstrated that patients with oral mucosal diseases are widely misdiagnosed, leading to multiple consultations and insufficient treatments.…”

Nonneoplastic diseases and disorders of the oral mucosa: A contemporary overview

“…This large group of diseases can affect the oral mucosa alone or in combination with skin lesions. Leuci et al discuss the most frequent autoimmune vesiculo‐bullous disorders: pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid and linear IgA disease. They provide a comprehensive account of classification, etiology, molecular pathogenesis, clinical features, diagnosis and management.…”