Oral Features of Mucocutaneous Disorders
Desquamative gingivitis is a clinical feature of a variety of diseases. It is characterized by epithelial desquamation, erythema, ulceration, and/or the presence of vesiculobullous lesions of gingiva and other oral tissues. This phenomenon can be a manifestation of a number of dermatoses, most commonly lichen planus, cicatricial pemphigoid (benign mucous membrane pemphigoid), and pemphigus vulgaris (Tables 1 and 2). Biopsy specimens obtained from mucosal lesions may sometimes provide equivocal histopathologic ﬁndings and are often inadequate as a single examination to establish the correct diagnosis because several diseases can produce a subepithelial blister. Therefore, direct immunoﬂuorescence examination is necessary to establish a definitive diagnosis. Oral lesions may occur ﬁrst or very early in several mucocutaneous disorders. Accurate diagnosis and effective treatment of these lesions may greatly diminish or reverse disease progression.
Lichen planus is a relatively common dermatologic disease that affects the skin and mucous membranes, including the oral cavity. Although the etiology of lichen planus is unknown, its immunologic features suggest a cell-mediated immune response to intraepithelial antigens. Lichen planus generally develops between the ages of 40 and 70, and it is more common in females than males. Skin and oral lesions of lichen planus in children are rare but have been reported. Oral manifestations occur in approximately 2.0% of the general population, while cutaneous lesions occur in 0.4%.14 Ten percent to 20% of patients with lichen planus demonstrate oral as well as cutaneous lesions.
Intraoral features of lichen planus include reticular, papular, plaque-like, atrophic, ulcerative, and bullous lesions. The reticular pattern occurs most frequently and is often seen as white lace-like lesions located bilaterally on the buccal mucosa. The reticular, plaque-like, and papular forms are generally asymptomatic and may require no treatment. Patients with these types of lesions may report a change in surface texture or roughness in the area that is affected. The atrophic, ulcerative, and bullous forms of the disease are referred to as erosive lichen planus. It is usually the onset of erosive lesions that motivates patients to seek treatment.
Patients often present with a combination of painful erosive lesions in conjunction with white lesions. Patients with erosive lichen planus may exhibit desquamative gingivitis and a positive Nikolsky’s sign, characterized by epithelial separation from the underlying connective tissue as a result of minor trauma. A small percentage of patients with lichen planus will experience transient small bullae or vesicles involving the mucosal surfaces.
In addition to the oral cavity, lesions may also be seen on the skin, esophagus, genitalia, and rarely the eyes. Skin lesions occur alone or in combination with intraoral lesions and present as recurrent violaceus, keratotic, pruritic patches. Vulvovaginal-gingival and peno-gingival syndromes refer to a variant of lichen planus that affects the gingiva as well as the genitourinary tract of either men or women.
In lichen planus, as well as other dermatologic diseases affecting the oral mucosa, biopsy specimens are essential in establishing a diagnosis for erosive and plaque-like forms and very helpful for reticular forms.
The histologic features of lichen planus include,
- 1. epithelial acanthosis and hyperkeratosis,
- 2. liquifaction degeneration of the epithelial basal cells,
- 3. saw-tooth rete ridges,
- 4. and a dense, band-like, sub-basilar inﬁltrate of T lymphocytes.
These classic histologic features are more commonly seen in skin biopsies, while mucosal biopsy specimens are often less distinctive in character. Although immunoﬂuorescence studies of lichen planus do not suggest pathognomonic features associated with the disease, direct immunoﬂuorescence examination may be of value in supporting the diagnosis or ruling out other diseases. A linear or a shaggy deposit of ﬁbrin or ﬁbrinogen at the basement membrane is often observed in biopsy specimens, which are examined using direct immunoﬂuorescence techniques. In addition, cytoid bodies are commonly seen at the epithelial-connective tissue interface and are thought to represent necrotic keratinocytes. Although the etiology remains elusive, these histologic and immunoﬂuorescence features suggest that the condition represents a cell-mediated autoimmune response to basal keratinocytes that express a foreign or altered self-antigen. This suggestion is supported by recent data which indicate that external substances such as mercury in dental amalgams may induce keratinocyte ICAM-1 expression, increased binding of T cells to normal keratinocytes, and increased production of TNF-α in vitro.
Lichenoid lesions resembling lichen planus may occur in association with the use of medications, including antimalarial drugs, anti-hypertensives, and non-steroidal anti-inﬂammatory agents. Lichenoid lesions demonstrate clinical, histologic, and immunoﬂuorescence patterns similar to idiopathic lichen planus, and they often resolve without recurrence following discontinuation of the identiﬁed medication.
Exposure to dental restorative materials and cinnamon flavoring agents has also been reported to induce lichenoid reactions. Lichen planus may be associated with systemic diseases including hypertension and diabetes mellitus as well as hepatitis B and C. Lesions identical to lichen planus are seen in patients with acute and chronic graft-versus-host disease and lupus erythematosus.
Treatment of oral lichen planus requires elimination of potential factors associated with lichenoid reactions, elimination or control of local irritants, and the effective use of therapeutic agents that suppress excessive lymphocyte function. Patients with erosive lichen planus are often successfully treated with corticosteroids. Topically applied medications such as ﬂuocinonide and clobetasol gel, beclomethasone dipropionate spray (inhaler), or dexamethasone mouthrinses are effective in inducing remission of lesions. Short-term tapering doses of systemic corticosteroids such as prednisone or intralesional injections are useful in severe episodes as well as in recalcitrant cases. Although expensive to use, systemic and topically administered cyclosporin has shown promising results. Recently, topical tacrolimus has been shown to be an effective form of treatment for oral lichen planus. Other medications such as griseofulvin, azathioprine, cyclophosphamide, dapsone, retinoids, metronidazole, levamisole, thalidomide, and low molecular weight heparin have shown some treatment efﬁcacy, but evidence based data are lacking. In addition, the potential for signiﬁcant side effects may limit their use. Periodontists who administer these drugs should be aware of reported side effects and be prepared to take appropriate action should any occur. A physician may need to be involved in diagnosis of associated systemic disease and in provision of systemic therapy. In these circumstances, coordinated follow-up involving both the dentist and physician is important. Although some patients experience complete remission following ther-apy, lichen planus is more often persistent/recurrent in nature and is likely to require periodic retreatment.
Controversy exists regarding the potential for malignant transformation in patients with lichen planus. Some clinical investigations have demonstrated an increased incidence of oral cancer in lichen planus lesions ranging from 0.4% to 5.6%. Others, how-ever, have questioned the validity of histologic features used to establish the initial diagnosis. Some early precancerous (dysplastic) lesions may present with lichenoid features, and create the impression of malignant transformation from preexisting lichen planus lesions. A recent systematic analysis, however, indicated that individuals with oral lichen planus may have a 10-fold increased risk of developing squamous cell carcinoma when compared to the general population. Regardless of the dispute, it is clear that regular recalls are important to assess the character of recurrent lichen planus or lichenoid lesions, and periodic biopsies are often necessary for areas that do not respond to treatment.
Mucous membrane pemphigoid
Chronic ulcerative stomatitis