ORAL LICHEN PLANUS

Oral lichen planus (OLP) is a common chronic immunologic inflammatory mucocutaneous disorder that varies in appearance from keratotic (reticular or plaquelike) to erythematous and ulcerative. About 28% of patients who have OLP also have skin lesions.The skin lesions are flat violaceous papules with a fine scaling on the surface. Unlike oral lesions, skin lesions are usually self-limiting, lasting only 1 year or less. The lack of sound epidemiologic studies and the variations in signs as well as symptoms make estimates of prevalence difficult.

Etiology and Diagnosis
The etiology of lichen planus involves a cell-mediated immunologically induced degeneration of the basal cell layer of the epithelium. Lichen planus is one variety of a broader range of disorders of which an immunologically induced lichenoid lesion is the common denominator.Thus, there are many clinical and histologic similarities between lichen planus and lichenoid dermatoses and stomatitides associated with drugs, some autoimmune disorders, and graft-versus-host reactions.Although lichen planus may manifest as a particularly well-defined and characteristic lesion, the differential diagnosis for less specific lesions is extensive. Speculated cofactors in causation, such as stress, diabetes, hepatitis C, trauma, and hypersensitivity to drugs and metals, have varying degrees of support, with the last three having the most convincing evidence.At the very least, some of these factors may add to the risk of developing OLP in susceptible patients.
As stated above, in “true” OLP a specific causative factor cannot be identified. However, clinical and microscopic changes that are consistent with OLP will often occur in response to a variety of agents (eg, drugs, chemicals, metals, and foods).When these manifestations take place, they are referred to as “lichenoid” reactions. When the offending agent or antigen is removed, the signs and symptoms are reversed; examples in reported cases include reactions to dental restorations, mouth rinses, antibiotics, gold injections for arthritis, and immunocompromised status such as graft-versus-host disease.These reactions are not to be confused with other hypersensitivity reactions such as urticaria or erythema multiforme, which differ both clinically and microscopically.
These often confusing clinical variations (Figure 5-34) mandate a thorough clinical work-up and histologic examination to rule out possible dysplasia and carcinoma. This requires not only an initial biopsy but also follow-up biopsies when changes in signs and symptoms occur.
(Because some lesions of oral lichen planus are erosive and others are bullous, this disorder is also discussed in Chapter 4. The emphasis in this chapter is on the white non-erosive nonbullous forms of lichen planus.)
Clinical Features
In general, studies of patients with OLP reveal that there is no evident genetic bias or uniform etiologic factor. The mean age of onset is the fifth decade of life, and there is clearly a female predominance. Although OLP may occur at any oral mucosal site, the buccal mucosa is the most common site. OLP may be associated with pain or discomfort, which interferes with function and with quality of life. Approximately 1% of the population may have cutaneous lichen planus. The prevalence rate of OLP ranges between 0.1 and 2.2%.
27,30,173,174
The skin lesions of lichen planus have been classically described as purple, pruritic, and polygonal papules.
OLP is classified as reticular (lacelike keratotic mucosal configurations), atrophic (keratotic changes combined with mucosal erythema), or erosive (pseudomembrane-covered ulcerations combined with keratosis and erythema) and bullous (vesiculobullous presentation combined with reticular or erosive patterns).Apart from the erosive and bullous forms of the disorder, reticular OLP is quite frequently an indolent and painless lesion that is usually asymptomatic before it is identified during a routine oral examination. The clinical features of the lesions in a given patient often vary with time, as does their extent and the area of erosion of the atrophic mucosa.The reticular form consists of (a) slightly elevated fine whitish lines (Wickham’s striae) that produce either a lacelike pattern or a patern of fine radiating lines or (b) annular lesions. This is the most common and most readily recognized form of lichen planus. Most patients with lichen planus at some time exhibit some reticular areas. The most common sites include the buccal mucosa (often bilaterally), followed by the tongue; lips, gingivae, the floor of the mouth, and the palate are less frequently involved. Whitish elevated lesions, or papules, usually measuring 0.5 to 1.0 mm in diameter, may be seen on the well-keratinized areas of the oral mucosa. However, even large plaquelike lesions may occur on the cheek, tongue, and gingivae, and these are difficult to distinguish from leukoplakia.
Bullous lichen planus (see Chapter 4) is rare and may sometimes resemble a form of linear IgA disease.
Atrophic lichen planus presents as inflamed areas of the oral mucosa covered by thinned red-appearing epithelium. Erosive lesions probably develop as a complication of the atrophic process when the thin epithelium is abraded or ulcerated. These lesions are invariably symptomatic, with symptoms that range from mild burning to severe pain.
ORAL LICHEN PLANUS

Papular, plaquelike, atrophic, and erosive lesions are very frequently accompanied by reticular lesions, a search for which is an essential part of the clinical evaluation in suspected cases of lichen planus. Characteristically, the affected areas of the oral mucosa are not bound down or rendered inelastic by lichen planus, and the keratotic white lines cannot be eliminated by either stretching the mucosa or rubbing its surface. Reticular papular lesions are generally asymptomatic; atrophic, erosive, and bullous forms are generally associated with pain.
Atrophic or erosive lichen planus involving the gingivae results in desquamative gingivitis (see Figure 5-34, B), a condition characterized by bright red edematous patches that involve the full width of the attached gingivae. Lichen planus must be distinguished histologically from other diseases that cause desquamative gingivitis, such as mucous membrane pemphigoid and pemphigus. Lichen planus has occasionally been described in association with autoimmune diseases.
Histopathologic Features
Three features are considered essential for the histopathologic diagnosis of lichen planus: (1) areas of hyperparakeratosis or hyperorthokeratosis, often with a thickening of the granular cell layer and a saw-toothed appearance to the rete pegs; (2) “liquefaction degeneration,” or necrosis of the basal cell layer, which is often replaced by an eosinophilic band; and (3) a FIGURE 5-34 Forms of lichen planus. A, Reticular lichen planus of the buccal mucosa. B, Atrophic lichen planus of the gingiva. C, Erosive lichen planus of the tongue.
dense subepithelial band of lymphocytes (Figure 5-35). Isolated epithelial cells, shrunken with eosinophilic cytoplasm and one or more pyknotic nuclear fragments (Civatte bodies), are often scattered within the epithelium and superficial lamina propria. These represent cells that have undergone apoptosis. The linear sub-basilar lymphocytic infiltration is composed largely of T cells. Immunohistochemical studies have confirmed that the T4/T8 ratio of the lymphocytes in the epithelium and lamina propria in lichenoid lesions is higher than in either normal or leukoplakic mucosa, thus providing an additional feature for distinguishing leukoplakia from a lichenoid reaction.
Immunofluorescent Studies
Immunofluorescent studies of biopsy specimens from lesions of lichen planus reveal a number of features that are not seen in hematoxylin-eosin (H&E)–stained sections and that both reflect the mode of development of these lesions and aid in distinguishing lichen planus from a number of other dermatoses. Direct immunofluorescence demonstrates a shaggy band of fibrinogen in the basement membrane zone in 90 to 100% of cases.Patients also may have multiple mainly IgM-staining cytoid bodies, usually located in the dermal papilla or in the peribasalar area. These cytoid bodies are considered to be highly suggestive of lichen planus if they are present in large numbers or grouped in clusters.

Differential Diagnosis
Differential diagnosis of lichen planus must consider the range of other lichenoid lesions (eg, drug-induced lesions, contact mercury hypersensitivity, erythema multiforme, lupus erythematosus, and graft-versus-host reaction), as well as leukoplakia, squamous cell carcinoma, mucous membrane pemphigoid, and candidiasis.A detailed history of the clinical appearance and distribution of the lesions is very helpful.
Although it does not always provide an unequivocal diagnosis, a biopsy should be carried out before treatment of the lesions, because of the tendency for corticosteroids to confuse the diagnosis. Asymptomatic reticular lichen planus is often left untreated, and biopsy is not usually performed. Biopsy of papular and plaquelike OLP should be performed to rule out dysplastic changes and leukoplakia. Biopsy is usually performed on the erosive and bullous forms, partly because they are symptomatic (and thus brought to the clinician’s attention) and partly to differentiate them from other vesiculobullous disorders.
Clinical Course and Prognosis
The lesions of OLP appear, regress, and re-appear in a somewhat unpredictable fashion. Andreasencalculated that 41% of reticular lesions healed spontaneously whereas 12% of atrophic lesions, 7% of plaquelike lesions, and 0% of erosive lesions healed without treatment. Silverman and Griffith
reported that when observed longer than 1 year, approximately 10% of a group of patients with predominantly erosive lesions had remissions. In a more recent, larger, and prospective study, Thorn and associates reported that papular and ulcerative (erosive) changes were short-term lesions whereas atrophic and plaquelike changes were characterized by many remissions and newly developing lesions. Thorn and co-workers demonstrated that long-term topical steroid and antimycotic therapy had no apparent effect on the course of the disease. Numerous reports have related lichenoid lesions to a contact sensitivity to mercury and, less often, gold and food flavorings.Removal of amalgam fillings in mercury-sensitive individuals who have contact-related lesions has almost always led to the complete resolution of the disease or at least to significant improvement.It must be stressed that lichenoid lesions that are caused by a contact allergy to dental materials such as amalgam occur only directly opposite the restoration. In patients with lichen planus, the general removal of amalgam fillings that are not directly opposite a lesion is not justified.
The status of OLP as a premalignant condition has been debated for many years. Numerous publications have described the clinical and histopathologic follow-up of lesions (in some cases, over many decades).The occurrence of squamous cell carcinoma in most series ranges from 0.4 to 2.0% per 5-year observation period.The most recent and extensive study reported a rate of 1.5% for patients observed over 7.5 years.
These rates are similar to those quoted for malignant change in leukoplakia and represent some 50 times the rate for the general population. OLP fulfills the criteria for a “premalignant” condition and was so designated at the 1984 International Seminar on Oral Leukoplakia and Associated Lesions Related to Tobacco Habits.Although malignant transformation is reported to be more likely in erosive lesions, possibly due to the exposure of deeper layers of the epithelium to oral environmental carcinogens, there appears to be no consistent clue to the identity of those lesions that are likely to become malignant. Several investigators have described a lesion (referred to as oral lichenoid dysplasia) on the basis of a defined histopathologic picture and have postulated that this lesion is an independent precancerous lesion that mimics lichen planus and represents the true precursor of malignant change in lichen planus.
There is no general agreement on the grading of lichen planus, either clinically or histopathologically. Therefore, continued surveillance, repeated biopsy, and (where possible) eradication of erosive lesions and those lesions demonstrating dysplastic changes remain the safest course. Most cases of squamous cell carcinoma arising in an area of lichen planus are found on the tongue.However, those cases of lichen planus exhibiting dysplastic changes are reportedly more prevalent on the buccal mucosa.
TreatmentThere is no known cure for OLP; therefore, the management of symptoms guides therapeutic approaches. Corticosteroids have been the most predictable and successful medications for controlling signs and symptoms. Topical and/or systemic corticosteroids are prescribed electively for each patient after orientation to OLP and by patient choice.Topical medications include high-potency corticosteroids, the most commonly used of which are 0.05% fluocinonide (Lidex) and 0.05% clobetasol (Temovate).These are frequently prescribed as pastes or as gels. The topical forms are applied daily to meet each patient’s needs. Topical steroids can be applied to the lesions with cotton swabs or (especially on the buccal mucosa) with gauze pads impregnated with steroid. In addition, extensive erosive lesions of OLP on the gingiva (desquamative gingivitis) may be treated effectively by using occlusive splints as carriers for the topical steroid. Long-term studies show no adverse systemic side effects with topical steroids, but occlusive therapy with high-potency steroids does cause systemic absorption, and patients should be carefully monitored and treated with the minimal amount of medication required to manage each individual.
Candida overgrowth with clinical thrush may develop, requiring concomitant topical or systemic antifungal therapy. Some studies have shown that the use of an antibacterial rinse such as chlorhexidine before steroid application helps prevent fungal overgrowth.
Systemic steroids are rarely indicated for brief treatment of severe exacerbations or for short periods of treatment of recalcitrant cases that fail to respond to topical steroids.
Systemic administration of prednisone tablets may be done with dosages varying between 40 and 80 mg daily for less than 10 days without tapering. The time and dosage regimens are determined individually, based on the patient’s medical status, severity of disease, and previous treatment responses. End points and stabilization of treatment are determined by each patient since symptoms are managed only to individual satisfaction or acceptance. Consultation with the patient’s primary care physician is important when underlying medical problems are present.Retinoids are also useful, usually in conjunction with topical corticosteroids as adjunctive therapy for OLP.
Systemic and topically administered beta all-trans retinoic acid, vitamin A acid, systemic etretinate, and systemic and topical isotretinoin are all effective, and topical application of a retinoid cream or gel will eliminate reticular and plaquelike lesions in many patients. However, following withdrawal of the medication, the majority of lesions recur. Topical retinoids are usually favored over systemic retinoids since the latter may be associated with adverse effects such as liver dysfunction, cheilitis, and teratogenicity.A new systemically administeredretinoid, temarotene, is reported to be an effective therapy for OLP and to be free of side effects other than a slight increase in liver enzymes.Other topical and systemic therapies reported to be useful, such as dapsone, doxycycline, and antimalarials, require additional research.Topical application of cyclosporine appears to be helpful in managing recalcitrant cases of OLP. Although this has been confirmed in double-blind trials, the cost of cyclosporine solution, its hydrophobicity and unpleasant taste, and the yet unanswered questions regarding the drug’s ability to promote viral reproduction and malignant change in epithelial cells have limited its use except for patients with extensive and otherwise intractable oral lesions.When lesions have been confined to the mucosa just opposite amalgam restorations and when patients have been positive for patch tests to mercury or other metals, complete removal of the amalgam restorations has been curative in most patients.Surgical excision is usually not indicated for the treatment of OLP except in cases where concomitant dysplasia has been identified.