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Lichen planus is a lichenoid autoimmune mucositis with a clinically different but microscopically similar dermal counterpart. On the skin the disease is usually of shorter duration, approximately 3 years, and does not have the ulcerating and blistering effects seen frequently in oral lesions. In the mouth lichen planus has several clinical variants with considerable cross-over between variants, and with occasional shifting from one variant to another. Some of these variants are thought to represent an elevated cancer risk but there is ongoing debate as to the validity of this hypothesis.
Some cases have obvious etiologic associations,
usually a systemic medication or mucosal contact with dental materials or
certain spices, but the etiology in most cases remains unknown. There is
no strong association between oral and dermal lesions and most persons with
oral involvement never have skin involvement. Oral lichen planus can be found
in 1/1,000 adults (Table 1).
Population studies have shown a similar prevalence rate for men and women, but clinical investigations have always found a relatively strong female predilection, usually with a 1:2 male:female ratio. All ages are affected but the disease is rare in children and is most likely to be first seen in young and middle-aged adults. The great majority of cases present as irregular bilateral plaques of the buccal mucosa, but any oral surface can be affected and occasional patients present with extensive involvement throughout the mouth. Lichen planus of the keratinized oral mucosa, such as gingiva, lingual dorsum and hard palate, may be so excessively keratinized that lesions are clinically indistinguishable from leukoplakia or frictional keratosis.
The most common oral presentation is a reticular or "spider web" pattern of slightly raised, white keratotic streaks, mistakenly termed Wickham's striae after the fine checkerboard pattern found on the dermal plaques of lichen planus (Figures 1 & 2). The intersecting white lines characteristically show numerous very fine perpendicular white lines along their length, and areas of intersection often have punctate nodules of keratin hyperplasia. Some individuals will show only these punctate nodules, while others will show serpiginous or circinate white lines, with or without a background of reticulated lines (Figures 3 & 4).
In addition to the keratotic changes, half of affected mucosa shows a diffuse background of mild to intense erythema which may extend some distance from the white lines (Figure 5). This red macule is poorly demarcated from the surrounding normal mucosa and apparently represents epithelial atrophy, allowing underlying vascular flow to become more visible. Occasional lesions are primarily erythematous, with very few white streaks, and these must be distinguished by biopsy from erythroplakia and erythroleukoplakia, as well as from oral psoriasis. Occasional lesions also will present with intermittent, sometimes severe, ulceration or blistering of the mucosa.
Most cases of lichen planus are asymptomatic,
but atrophic and ulcerative cases may be somewhat tender and sensitive to
abrasive contacts or acidic foods. The pruritus so common to the dermal lesions
is not present in the oral lesions. The clinician must be diligent in the
attempt to relate the oral lesion to adjacent dental materials or a patient
habit, such as chewing gum with cinnamon or peppermint flavoring. When a
specific contact hypersensitivity is suspected, the diagnostic term lichenoid reaction
is preferred. The clinician must also be diligent
in his or her search for induration, ulceration and other clinical signs
of malignancy. These features of lichen planus are discussed elsewhere in
the text under that title.
Pathology and Differential Diagnosis
Oral lichen planus, like its dermal counterpart, is characterized by a subepithelial band of chronic inflammatory cells, predominantly lymphocytes, which has a lower border well-demarcated from deeper connective tissues (Figure 6). When plasma cells or Langerhans cells are numerous, lichenoid reaction rather that autoimmune lichen planus should be suspected. If the biopsy is performed during an episode of quiescent activity, this band of infiltrate might be quite sparse and if a stria is cut cross-wise the band will appear as a subepithelial lymphoid aggregate.
Liquefactive or ballooning degeneration of cells of the basal and suprabasal layers is also characteristic of lichen planus (Figure 7), although it may be patchy and minimally present. Degenerated apoptotic cells may be seen in the epithelium and occasional cases will show eosinophilic colloid or Civatte bodies between the spinous cells. Patchy areas often demonstrate squamoid change of basal cells and rete ridges may show one of two patterns: complete loss of the ridges with flattening of the inferior surface of the epithelium, or a morphologic shift into an inverted triangle or "saw-toothed" ridge (Figure 8), as is more frequently seen in the skin counterpart. Many cases will show a thickened or hyalinized basement membrane, perhaps with scattered clear microvesicles, and in dark-skinned individuals melanin pigmentation may be seen within and beneath the basal cell layer (pigment incontinence).
Bullous lichen planus is represented by blister formation at the level of the basement membrane (Figure 9), and ulcerative lichen planus will show typical inflammatory degeneration and necrosis of epithelium adjacent to the ulcer. In the latter, no epithelium remains along the ulcer bed itself, and in the former, small epithelial tags may be seen to lift away from the basement membrane at the ulcer edge. When lesions are ulcerated, the lichenoid band of inflammatory cells may be replaced by the more randomly distributed chronic and acute inflammatory cells of granulation tissue. The band is still present beneath bullous lesions for several hours after the blister has ruptured.
The surface is excessively keratinized by parakeratin, orthokeratin, or a combination thereof, except in the most atrophic cases. On mucosal surfaces which are normally heavily keratinized, this keratin hyperplasia may represent more than half of the entire epithelial thickness and may show short, pointed surface projections similar to those seen in verruciform leukoplakia. Hyperplastic lichen planus is the term used for such a phenomenon (Figure 10). The granular cell layer may become pronounced, but only in lesions with secondary frictional trauma of long duration.
The pathologist must always be careful to evaluate the basal epithelium for evidence of dysplasia, especially in atrophic and ulcerated cases. When dysplasia is found it is graded as it would be without the surrounding lichenoid changes but the diagnosis is often changed to lichenoid dysplasia. It is not yet known whether such cases represent transformation of a true lichen planus or an unusual T-cell response to altered basal cells.
The differential diagnosis of intraoral lichen planus includes the aforementioned lichenoid dysplasia and contact stomatitis or lichenoid reaction. Distinguishing features of lichenoid drug reaction include infiltration of lymphocytes high into the epithelium, quite pronounced liquefactive degeneration of basal cells, and loss of the sharp demarcation of the lower margin of the infiltrated band.
Cases with very thick subepithelial immunologic infiltrates, especially those with lymphoid aggregates deep in subepithelial connective tissues are more likely associated with hypersensitivity reactions, as are lesions with numerous plasma and Langerhans cells. Deep aggregates may, moreover, be perivascular, may contain germinal centers, and may be indicative of a secondary candidiasis or a systemic lichenoid disease such as lupus erythematosus. Because of the latter associations, fungal stains should be used, especially if there are neutrophils in the keratin layers, and signs of vasculitis should be sought, although a negative result in either examination does not necessarily rule out yeast or systemic autoimmunity.
Another lichenoid mucositis to be considered in the differential diagnosis is graft-vs.-host disease (GVHD), which likely has a common pathoetiology in T-cell damage to the epithelium. The lymphocytic band in GVHD is usually more sparse and less well-defined than that of idiopathic lichen planus, and marked fibrosis of subepithelial stroma is common in long-standing cases. Subepithelial blistering is rare except during acute stage disease, in which case skin involvement is quite likely and greatly aids in the diagnosis. It is important to remember that almost all individuals with GVHD demonstrate some form of oral involvement, slight though it may be.
Direct immunofluorescence is of some value in the differential diagnosis of lichen planus, but it is seldom used because other features are adequate to the task. In more than 3/4 of all cases there is a slightly irregular linear deposition of fibrinogen along the basement membrane. This rather nonspecific change is not diagnostic in and of itself but can be quite helpful, when combined with the clinical features and with the absence of immunoglobulin or complement reactivity, to rule out other autoimmune disorders such as pemphigoid and lupus erythematosus. The pathologist must be cautious, however, as occasional patchy complement-associated immunofluorescence may be seen in the basement membrane adjacent to an ulcerative or atrophic area of lichen planus.
Discoid and systemic lupus erythematosus may present with oral keratotic and ulcerative lesions which are clinically identical to lichen planus and show a strong histopathologic similarity as well. Elongated, thin rete ridges are more likely to be associated with lupus, as is deep extension of the subepithelial lymphocytic band, especially with lymphoid aggregates present. Rete hyperplasia in lupus may, in fact, be so extensive that dyskeratosis occurs and the epithelium takes on the localized appearance of pseudoepitheliomatous hyperplasia. Thickened or degenerated endothelium with perivascular infiltrates is, of course, very helpful for the identification of lupus vasculitis, but these changes are often missing in oral examples. Cutaneous lupus lesions usually show a positive IgG and IgA reactivity along the basement membrane, and a patchy band of complement reactivity may be seen on immunofluorescence. Circulating anti-nuclear antibodies may also be present in cases of systemic disease, but an extensive discussion of the extraoral characteristics of lupus is beyond the scope of the present chapter.
Lichen sclerosus et atrophicus is the final lesion to differentiate from oral lichen planus. Extremely rare in the mouth, this typically genital mucositis may be clinically indistinguishable from oral lichen planus. The epithelium is uniformly atrophic, often extremely so, and only a thin layer of surface keratin is seen. There is typically extensive subepithelial fibrosis or hyalinization and a lesser inflammatory infiltrate is noticed; the infiltrate is often separated from the epithelium by a hyalinized band. Subepithelial hyalinization is also a feature of systemic sclerosis or scleroderma, amyloidosis and oral submucous fibrosis. Congo red birefringence and thioflavin T fluorescence can help to rule out amyloidosis, but differences in clinical features may be needed to rule out the other disorders.
Treatment and Prognosis
There is no cure for this disease and therapy is only palliative. Fortunately, oral lichen planus lesions wax and wane, and are typically asymptomatic. For those patients suffering from tenderness and sensitivity to acidic foods, topical or systemic prednisolone is usually effective but should be used sparingly because of the potential systemic side effects. Persons affected with oral lesions seldom develop skin lesions, although the clinician should be on the lookout for evidence of lupus erythematosus during follow-up examinations, especially in patients with arthritic joint pains.
For patients with atrophic or ulcerative or bullous forms of the disease, an examination for early oral cancer should be performed every 4-6 months. This follow-up may entail repeat biopsies of areas of unhealing ulceration, induration or deep erythema. The estimated risk of malignant transformation, if real, is less than 2% over a 10 year period. Lichen sclerosus et atrophicus of the mouth carries no malignant potential, as it does in the genital region.
References (Chronologic Order)
Note: For general references click on link to the left.
Schubert MM, Sullivan KM, Morton TH, et al. Oral manifestations of chronic graft vs host disease. Arch Intern Med 1984; 133:1591-1595.
Rhodus NL, Johnson DK. The prevalence of oral manifestations of systemic lupus erythematosus. Quintessence Internat 1990; 21:461-465.
Vincent SD, Fotos PG, Baker KA, Williams TP. Oral lichen planus: the clinical, historical and therapeutic features of 100 cases. Oral Surg Oral Med Oral Pathol 1990; 70:165-171.
Silverman S Jr. Lichen planus. Curr Opin Dent 1991; 1:769-772.
Eisenberg E. Lichen planus and oral cancer: is there a connection between the two? J Am Dent Assoc 1992; 12:104-108.
Torres V, Mano-Azul AC, Correia T, Soares AP. Allergic contact cheilitis and stomatitis from hydroquinone in an acrylic dental prosthesis. Contact Dermatitis 1993; 29:102-103.
Zegarelli DJ. The treatment of oral lichen planus. Ann Dent 1993; 52:3-8.
Batsakis JG, et al. Lichen planus and lichenoid lesions of the oral cavity. Ann Otol Rhinol Laryngol 1994; 103:495-497.
Bricker SL. Oral lichen planus: a review. Semin Dermatol 1994; 13:87-90.
Sanchis-Bieslsa JM, et al. Oral lichen planus. An evolutive clinical and histological study of 45 patients followed up on for five years. Bull Group Int Rech Sci Stomatol Odontol 1994; 37:45-49.
Veien NK, Borchorst E, Hattel T, Laurberg G. Stomatitis or systemically-induced contact dermatitis from metal wire in orthodontic materials. Contact Dermatitis 1994; 30:210-213.
Nakamura S, Hiroki A, Shinohara M, et al. Oral involvement in chronic graft-versus host disease after allogenic bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1996; 82:556-563.
Porter SR, Kirby A, Olsen I, Barrett W. Immunologic aspects of dermal and oral lichen planus. Oral Surg Oral Med Oral Pathol 1997; 83:358-366.
Scully C, Beyli M, Feirrero M, Ficarra G, et al. Update on oral lichen planus: aetiopathogenesis and management. Crit Rev Oral Bio Med 1998; 9:86-122.
McCreary CE, McCarter BE. Clinical management of oral lichen planus. Brit J Oral Maxillofac Surg 1999; 37:338-343.
Table 1: Gender-specific prevalence rates per 1,000 population for selected oral masses and surface alterations in U.S. adults, ranked by total frequency. Modified from Bouquot JE. Common oral lesions found during a mass screening examination. J Am Dent Assoc 1986; 112:50-57, and Bouquot JE, Gundlach KKH. Oral exophytic lesions in 23,616 white Americans over 35 years of age. Oral Surg Oral Med Oral Pathol 1986; 62:284-291.
* total examined population = 23,616 adults over 35 years of age
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