Diseases of the oral mucous membranes

Many systemic diseases have manifestations on the oral mucous membranes. In this review, we discuss a prototypical disease, lichen planus (LP), in detail. Oral lichen planus (OLP) is common, affecting 1% to 2% of the population. At least one third of these patients have LP skin disease. LP is intriguing to immunologists because of its clinical and histopathologic resemblance to chronic graft-versus-host reaction, systemic drug reactions, and allergic contact stomatitis to metals used in dental restorations. More recently, OLP, particularly the severe, recalcitrant, erosive type, has been associated with chronic hepatitis C infections and internal neoplasms such as thymoma and lymphoma. Lichen planus pemphigoides is a disease with coexisting features of both LP and bullous pemphigoid (BP). Most patients have an autoantibody directed against the 180 kDa minor BP hemidesmosomal antigen, but some patients also react to a unique 200 kDa antigen. Cicatricial pemphigoid (CP) is similar, in that the primary lesion is a subepithelial blister, but the oral and ocular mucous membranes are predominantly affected, with a tendency toward scarring. In CP, the autoantigens are heterogeneous; in about half of the cases, the 180 or 230 kDa BP antigens (or both) are identified in the lamina lucida. Some patients react to an antigen in the lower lamina lucida overlying the lamina densa, which corresponds to epiligrin, and more specifically, the 165 kDa α subunit of laminin 5. Pemphigus vulgaris (PV) and paraneoplastic pemphigus (PNP) are true autoimmune diseases, because the circulating antibodies are believed to be pathogenic. The prognosis for PV has improved dramatically since the corticosteroid era, but ~10% of patients still die of disease or complications of therapy. The PV antigen is a 130 kDa cadherin in the desmosome of epithelial cells. Interference with its function or assembly causes cells to separate and form acantholytic cells and intraepithelial blisters. PNP is usually associated with lymphoproliferative malignancies and demonstrates an array of autoantibodies directed against antigens of the adhering junctions: desmoplakins, PV antigen and other desmosomal proteins, and the major BP antigen. The mortality of PNP is >90% because of the combination of neoplasia and severe mucocutaneous disease. The treatment for all of the foregoing diseases includes corticosteroids in one of the forms, topical or systemic, with or without steroid-sparing agents, mainly dapsone, azathioprine, cyclophosphamide, and cyclosporine. The remainder of the essay is devoted to a brief discussion of selected developmental diseases that are rare but of extreme importance because of pathognomonic oral or cutaneous manifestations and sometimes “preventable” consequences, for example, dyskeratosis congenita (oral cancer); Papillon-LeFevre syndrome (loss of teeth); nevoid basal cell carcinoma syndrome (skin cancer); and Cowden's syndrome (breast cancer). Finally, a list of common infectious diseases occurring in both the normal and HIV-infected population is considered, followed by the unique associations of Kaposi's sarcoma and non-Hodgkin's lymphoma in patients with AIDS that may be the consequence of a new human herpes virus and Epstein-Barr virus, respectively.