Oral Biosci Med 1 (2004), No. 1 10. Mar. 2004
Oral Biosci Med 1/2004, S. 21-28
The Diagnosis and Management of Oral Lichen Planus: a Consensus Approach
/ Drore Eisen
/ Crispian Scully
Lichen planus (LP) is a common oral disorder, reviewed at an international meeting between the American Academy of Oral Medicine (AAOM) and International Federation of Oral Medicine (IFOM) in Montreal, Canada in 2001. This paper is a summary of the proceedings of that meeting.
Oral LP is of uncertain etiopathogenesis. Diagnosis is mainly on clinical grounds. Since there is still no conclusive evidence relevant to the etiology, therapy has traditionally attempted to suppress symptoms rather than to address the basic issues of susceptibility and prevention.
Symptomatic relief can be achieved in the majority of patients with topical corticosteroids alone, or other immunomodulatory topical agents, or combinations. Only infrequently do patients require the prolonged use of intralesional or systemic medications to control the disease process.
lichen planus, oral, etiopathogenesis, diagnosis
Lichen planus (LP) is a common chronic oral inflammatory disease, which can affect skin, nails, scalp and other mucosae. The prevalence is between 0.1 and 4 percent (Axell and Rundquist, 1987; Bouquot and Gorlin, 1986). LP is most frequent in the 40 to 70 years age range (Salem, 1989), and females predominate in a proportion of about two-to-one (Silverman et al, 1985; Thorn et al, 1988).
LP may represent a type IV hypersensitivity response to an antigen that could have altered keratinocyte function (Porter et al, 1997). It is a clinical and histological reaction to a variety of heterologous stimuli (Eversole, 1997).There is a cell-mediated immune response to epithelial-associated antigen, and the submucosal leukocyte population is predominantly T lymphocytic (Toto and Nadimi, 1987) with both CD4- and CD8-positive cells submucosally, and CD8 cells in the epithelium (Toto and Nadimi, 1987). T cells migrate to the oral epithelium mediated by adhesion molecules (ICAM-1 and VCAM). Upregulation of ELAM-1, ICAM-1, and VCAM-1 (especially by endothelial cells in the subepithelial vascular plexus) could play a role in the pathogenesis of LP (Regezi et al, 1996). Chemokines (Sugerman et al, 1996) (IL-1, -8, -10, -12 and TNF), secreted by keratinocytes are chemotactic for lymphocytes. Tumor necrosis factor-alpha (TNF-alpha), a cytokine involved primarily in T-cell-mediated immunopathological reactions, is implicated since it is found in diseases which bear clinical and histological similarities to LP (Simark-Mattsson et al, 1999).
In addition, there is upregulation of epithelial basement membrane extracellular matrix (ECM) proteins, including collagen types IV and VII, laminin and certain integrins - serving as pathways for T cell migration (Eversole, 1997). T cells then bind to keratinocytes and programmed cell death (apoptosis) is implicated in the basal cell destruction of LP (Dekker et al; Bloor et al, 1999; Majorana et al, 1999; Tanda et al, 2000).
Genetic background: familial LP is rare, and no studies have shown significant association with any particular HLA antigen (Mahood, 1983; Grunnet and Schmidt, 1983).
Infectious agents: an infective role remains speculative (Scully et al, 1998).
Liver disease: there is an association of LP and HCV in southern Europe and in Japan (Dupin et al, 1997; Bagan et al, 1998; Ingafou et al, 1998; Lodi et al, 1997; Arrieta et al, 2000; Carrozzo et al, 1999; del Olmo et al, 2000; Grote et al, 1998; Grote et al, 1999; Kirby et al, 1998; Lodi et al, 2000; Mignogna et al, 1998; Mignogna et al, 2000; Nagao et al, 1998; Nagao et al, 1999; Nagao et al, 2000b; Nagao et al, 2000a; Roy et al, 2000; van der Meij and van der Waal, 2000; Varela et al, 2000). No logical explanation for this has been established and no such association is seen in British (Ingafou et al, 1998), German (Grote et al, 1999), Irish (Roy et al, 2000), or Dutch (van der Meij and van der Waal, 2000) patients.
Stress: it has not been established whether the observed psychological alterations constitute a direct etiologic factor, or whether such alterations are a consequence of the disease (Rojo-Moreno et al, 1998).
Lichen planus often affects the oral mucosa, and lesions can occur without skin lesions; 20% of patients with oral lesions also have extraoral lesions (Silverman et al, 1985), while approximately 50% of patients with skin lesions also have oral LP. Eisen (1999) found extraoral manifestations included cutaneous LP in 16% of patients, genital LP in 19% of women and 4.6% of men. Oral LP is most common in the buccal mucosa, tongue and gingiva; and usually bilateral. Andreasen (1968) recognised reticular, papular, atrophic, ulcerative or erosive, plaque-like and bullous forms. Others distinguish three groups: reticular, atrophic and erosive (Silverman et al, 1985; Lozada-Nur and Miranda, 1997a). The ulcerative form is most likely to cause symptoms, from spontaneous soreness to severe pain accentuated by local irritants and trauma. Atrophic forms are quite common on the gingivae, constituting one form of desquamative gingivitis (Scully and Porter, 1997).
Lichenoid reactions (LR) are lesions with an identifiable etiology but clinically and histologically so similar to LP that, in many cases, differentiation is difficult or impossible (McCartan and McCreary, 1997).
In a few cases contact with amalgam can cause lichenoid reactions (Yiannias et al, 2000; Koch and Bahmer, 1999; Cederbrant et al, 1999; Camisa et al, 1999; Ostman et al, 1996; Bratel et al, 1996), and occasionally the lesions improve after substitution by some other restorative material (Bratel et al, 1996).
Lichenoid Drug Reactions (LDR)
Drugs reported to cause lichenoid reactions include non-steroidal anti-inflammatory drugs (NSAIDs), the angiotensin-converting enzyme inhibitors (ACEIs), antimalarials and gold (McCartan and McCreary, 1997).
The diagnosis of oral LP should not be based solely on the clinical aspects since it can mimic disorders such as keratoses, lupus erythematosus and even carcinoma. A histological diagnosis is therefore essential, the histopathological criteria being (Andreasen, 1968):
• Hyperortho- or hyperparakeratosis in reticular lesions, and epithelial thinning in atrophic clinical lesions. In the erosive form, the epithelium becomes detached, leaving an exposed connective tissue surface
• Degenerative changes of the basal cells
• A band-like subepithelial infiltrate of lymphocytes and histiocytes.
However, the histopathological assessment, based on the available WHO definition, is rather subjective and insufficiently reproducible (van der Meij and van der Waal, 2003) and stricter diagnostic criteria are required. Immunofluorescence studies may be helpful. Direct immunofluorescence (IFD) shows the basal lamina staining positively for fibrinogen - a protein not normally seen there. Immunofluorescence projects downwards into the submucosa, producing a stalactite appearance (Eversole, 1997; Schiodt et al, 1981; Gombos et al, 1992; Okochi et al, 1990; Hintner et al, 1990).
Using indirect immunofluorescence (IIF), a subpopulation of patients has been shown to have circulating antibodies that bind to cytoplasm of basal keratinocytes. This phenomenon was said to be more prevalent in lichenoid drug reactions (Lamey et al, 1995) but the same workers reported that lichen planus-specific antigen is not a useful marker to distinguish oral lichenoid drug eruptions from idiopathic LP (McCartan and Lamey, 2000).
The identification of lichenoid reactions is difficult. Unilateral lesions (Lamey et al, 1995) with erosive components have been reported to be more frequently lichenoid (Potts et al, 1987) though this is not always the case. Histologically, lichenoid drug reactions exhibit a more diffuse lymphocytic infiltrate, with eosinophils and plasma cells, and there may be more colloid bodies than in idiopathic oral LP. However, those findings are also not diagnostic. The most reliable diagnostic feature of lichenoid reactions is that they remit on withdrawal and reappear on rechallenge (Scully et al, 1998).
The possibility that the lesions may be lichenoid reactions should be considered before initiating therapy (Bolewska et al, 1990). When identified, such lesions can sometimes show considerable improvement after replacement of the offending restorations (Finne et al, 1982) or drug (Potts et al, 1987; Robertson and Wray, 1992).
The Koebner phenomenon, whereby lesions develop in response to trauma, is common in LP (Eisen, 1993b). Thus, eliminating or correcting causative factors such as sharp or rough dental restorations, fractured teeth, poorly fitting dental appliances and oral habits such as cheek biting may be beneficial. The institution of an optimal oral hygiene program which eliminates dental plaque and calculus can also improve gingival LP (Holmstrup et al, 1990).
Patients with oral LP are managed with medications that were neither developed nor intended for oral diseases and, consequently, most lack adequate efficacy studies. Thus such factors as optimal dose, duration of treatment, safety, and true efficacy remain unknown (Scully et al, 2000).
Bioadhesive gels such as cyanoacrylate and hydroxy ethylcellulose, and bioadhesive polymers such as chitosan have been utilized in the oral cavity as mechanical barriers that provide pain relief from oral ulcerations including those of oral LP. Additionally, when combined with topical corticosteroids, these agents have been employed as a method of improving the local delivery of these drugs by increasing their retention at the application site, increasing drug penetration, and increasing patient acceptability. Although frequently employed in practice, a controlled study suggests that topical steroids in adhesive bases are no more effective than the base preparations (Voute et al, 1993).
A variety of topical preparations and mouthwashes have been utilized to ameliorate the pain from oral erosive diseases. Various formulations containing one or more active ingredients, including anaesthetics, antimicrobials, wound cleansers, coating agents and occlusive dressings, are widely available. Although many of these products, as claimed, reduce the pain, their benefits are modest and short in duration.
The most commonly employed and useful agents for the treatment of LP are topical corticosteroids (Table 1). Studies utilizing midpotency and superpotent corticosteroids have demonstrated the efficacy of these in 30%-75% of patients (Carrozzo and Gandolfo, 1999; Lozada-Nur and Miranda, 1997b).
Table 1 Suggested topical corticosteroids for control of OLP
triamcinolone acetonide 0.1%
clobetasol propionate 0.05%
fluocinolone acetonide 0.025%
betamethasone dipropionate 0.05%
betamethasone valerate 0.1%
halobetasol propionate 0.05%
Therapy should be initiated with a potent preparation to achieve a rapid response. It is advisable to lower the strength of the preparation as soon as erosions re-epithelialize and erythematous lesions become asymptomatic.
Once the disease becomes inactive i.e. absence of lesions, or presence of only white reticular lesions, therapy may be temporarily discontinued.
Patients should be warned about the off-label use of topical corticosteroids and the accompanying package inserts which state for 'external use only'. Although a number of studies have demonstrated the safety of topical corticosteroids when applied to mucous membranes for short intervals (Plemons et al, 1990; Lehner and Lyne, 1969), the potential for adrenal suppression with prolonged use necessitates careful and frequent follow-up. Furthermore, as many as one third of LP patients treated with topical corticosteroids develop secondary candidiasis (Vincent et al, 1990).
For intractable erosive LP lesions, intralesional steroids such as triamcinolone acetonide (10-20 mg/ml) injections can be highly effective and repeated every 2-4 weeks (Table 2). Other steroids such as hydrocortisone may also be used but there are no studies to suggest which steroid is preferable. Frequent injections of steroids, however, may result in an unwanted systemic dose.
Table 2 Some topical and systemic treatment options for OLP patients
Potential Adverse Effects
Secondary candidiasis, systemic absorption, tachyphylaxis
Systemic absorption, pain, atrophy
Cushing's syndrome and suppression of the hypothalamic-pituitary-adrenal axis
Irritation, burning, teratogenic, photosensitivity, pigmentary changes
Erosions may worsen, rashes, teratogenic, cheilitis, dermatitis, photosensitivity, myalgias, intracranial hypertension, blood chemistry and lipid level abnormalities
Ocular toxicity, gastrointestinal, complete blood count abnormalities
Burning, accumulation of waxy particles, systemic absorption and nephrotoxicity
Bone marrow suppression, increase risk of infection and malignancy, hepatic and renal damage, numerous other adverse effects
Stinging. Systemic absorption and nephrotoxicity
Systemic corticosteroids should be reserved for recalcitrant severe erosive or erythematous LP, where topical approaches have failed, or for widespread oral LP with concomitant skin, genital, esophageal, or scalp involvement, and should only be administered by a Specialist. Daily doses of prednisone in the range of 40-80 mg are usually sufficient to achieve a response without the need for higher doses as in other mucocutaneous diseases such as pemphigus or pemphigoid. The toxicity of prednisone requires that it be used only when necessary, at the lowest dose possible and for the shortest duration of time. Therefore, prednisone should either be administered for very brief periods of time i.e. less than 5-7 days and then abruptly withdrawn, or the dose should be reduced by 5-10mg/day gradually over a 2-4 week period. If patients are able to tolerate alternate day administration of the same total dose, adverse effects may be minimized.
Additional Topical Treatment Options
The topical use of cyclosporine (ciclosporin) may be used as an adjunct to topical corticosteroids (Eisen et al, 1990; Harpenau et al, 1995). The standard solution (100 mg/ml) intended for systemic use in organ transplant recipients may be used as a mouthrinse in oral LP. The solution is prohibitively expensive for routine use and should be reserved for patients who are symptomatic. Topical retinoids such as tretinoin have been reported to be effective for oral LP (Sloberg et al, 1979). Retinoids applied to the skin often cause considerable irritation and inflammation, and the same is to be expected when applied to oral mucous membranes. Cheilitis is common.
Additional Systemic Treatment Options
None of the systemic drugs used for LP result in long-term remission and the disease usually recurs when they are withdrawn. Nevertheless, despite these shortcomings, systemic agents usually generate significantly better results than topical agents alone. A range of systemic agents may be employed for the treatment of oral LP in patients who are unresponsive to topical agents. All these drugs require monitoring for laboratory abnormalities and should be administered only by specialists familiar with their adverse effects.
Hydroxychloroquine may be used to control LP at daily doses of 200-400 mg (Eisen, 1993a). The systemic retinoids, acitretin (Laurberg et al, 1991),and isotretinoin (Camisa et al, 1999) can be beneficial when administered to patients with erosive LP. Several immunosuppressive agents can be employed for severe LP including azathioprine (100-150 mg/day), ciclosporin (2-4 mg/kg/day) and mycophenolate (2-3 gm/day).
A list of treatment options and adverse effects is summarized in Table 2, including topical immunosuppressives, introduced subsequent to this symposium. Tacrolimus, a steroid-free topical immunomodulator specifically developed as treatment for atopic dermatitis, has been reported to benefit patients with erosive LP, and has a good safety record (Vente et al, 1999; Olivier et al, 2002; Morrison et al, 2002; Rozycki et al, 2002; Kaliakatsou et al, 2002). Pimecrolimus, a similar agent, also shows promise (Ling, 2001).
- Andreasen JO. Oral lichen planus. 1. A clinical evaluation of 115 cases. Oral Surg Oral Med Oral Pathol 1968;25:31-42.
- Arrieta JJ, Rodriguez-Inigo E, Casqueiro M, Bartolom J, Manzarbeitia F, Herrero M et al. Detection of hepatitis C virus replication by in situ hybridization in epithelial cells of anti-hepatitis C virus-positive patients with and without oral lichen planus. Hepatology 2000;32:97-103.
- Axell T, Rundquist L. Oral lichen planus - a demographic study. Community Dent Oral Epidemiol 1987;15:52-56.
- Bagan JV, Ramon C, Gonzalez L, Diago M, Milian MA, Cors R et al. Preliminary investigation of the association of oral lichen planus and hepatitis C. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:532-536.
- Bloor BK, Malik FK, Odell EW, Morgan PR. Quantitative assessment of apoptosis in oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:187-195.
- Bolewska J, Holmstrup P, Moller-Madsen B, Kenrad B, Danscher G. Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. J Oral Pathol Med 1990;19:39-42.
- Bouquot JE, Gorlin RJ. Leukoplakia, lichen planus, and other oral keratoses in 23,616 white Americans over the age of 35 years. Oral Surg Oral Med Oral Pathol 1986;61:373-381.
- Bratel J, Hakeberg M, Jontell M. Effect of replacement of dental amalgam on oral lichenoid reactions. J Dent 1996;24:41-45.
- Camisa C, Taylor JS, Bernat JR Jr, Helm TN. Contact hypersensitivity to mercury in amalgam restorations may mimic oral lichen planus. Cutis 1999;63:189-192.
- Carrozzo M, Gandolfo S. The management of oral lichen planus. Oral Dis 1999;5:196-205.
- Carrozzo M, Gandolfo S, Lodi G, Carbone M, Garzino-Demo P, Carbonero C et al. Oral lichen planus in patients infected or non-infected with hepatitis C virus: the role of autoimmunity. J Oral Pathol Med 1999;28:16-19.
- Cederbrant K, Gunnarsson LG, Hultman P, Norda R, Tibbling-Grahn L. In vitro lymphoproliferative assays with HgCl2 cannot identify patients with systemic symptoms attributed to dental amalgam. J Dent Res 1999;78:1450-1458.
- Dekker NP, Lozada-Nur F, Lagenaur LA, MacPhail LA, Bloom CY, Regezi JA. Apoptosis-associated markers in oral lichen planus. J Oral Pathol Med 1997;26:170-175.
- del Olmo JA, Pascual I, Bagan JV, Serra MA, Escudero A, Rodriguez F et al. Prevalence of hepatitis C virus in patients with lichen planus of the oral cavity and chronic liver disease. Eur J Oral Sci 2000;108:378-382.
- Dupin N, Chosidow O, Lunel F, Fretz C, Szpirglas H, Frances C. Oral lichen planus and hepatitis C virus infection: a fortuitous association? Arch Dermatol 1997;133:1052-1053.
- Eisen D. Hydroxychloroquine sulfate (Plaquenil) improves oral lichen planus: An open trial. J Am Acad Dermatol 1993a;28:609-612.
- Eisen D. The therapy of oral lichen planus. Crit Rev Oral Biol Med 1993b;4:141-158.
- Eisen D. The evaluation of cutaneous, genital, scalp, nail, esophageal, and ocular involvement in patients with oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:431-436.
- Eisen D, Ellis CN, Duell EA, Griffiths CE, Voorhees JJ. Effect of topical cyclosporine rinse on oral lichen planus. A double-blind analysis. N Engl J Med 1990;323:290-294.
- Eversole LR. Immunopathogenesis of oral lichen planus and recurrent aphthous stomatitis. Semin Cutan Med Surg 1997;16:284-294.
- Finne K, Goransson K, Winckler L. Oral lichen planus and contact allergy to mercury. Int J Oral Surg 1982;11:236-239.
- Gombos F, Serpico R, Gaeta GM, Budetta F, De Luca P. The importance of direct immunofluorescence in the diagnosis of oral lichen planus. A clinical study and proposal of new diagnostic criteria. Minerva Stomatol 1992;41:23-32.
- Grote M, Reichart PA, Berg T, Hopf U. Hepatitis C virus (HCV)-infection and oral lichen planus. J Hepatol 1998;29:1034-1035.
- Grote M, Reichart PA, Hopf U. Increased occurrence of oral lichen planus in hepatitis C infection. Mund Kiefer Gesichtschir 1999;3:30-33.
- Grunnet N, Schmidt H. Occurrence of lichen planus in a family. Genetic susceptibility or coincidence? Clin Exp Dermatol 1983;8:397-400.
- Harpenau LA, Plemons JM, Rees TD. Effectiveness of a low dose of cyclosporine in the management of patients with oral erosive lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;80:161-167.
- Hintner H, Sepp N, Dahlback K, Dahlback B, Fritsch P, Breathnach SM. Deposition of C3, C9 neoantigen and vitronectin (S-protein of complement) in lichen planus pemphigoides. Br J Dermatol 1990;123:39-47.
- Holmstrup P, Schiotz AW, Westergaard J. Effect of dental plaque control on gingival lichen planus. Oral Surg Oral Med Oral Pathol 1990;69:585-590.
- Ingafou M, Porter SR, Scully C, Teo CG. No evidence of HCV infection or liver disease in British patients with oral lichen planus. Int J Oral Maxillofac Surg 1998;27:65-66.
- Kaliakatsou F, Hodgson TA, Lewsey JD, Hegarty AM, Murphy AG, Porter SR. Management of recalcitrant ulcerative oral lichen planus with topical tacrolimus. J Am Acad Dermatol 2002;46:35-41.
- Kirby AC, Lodi GL, Olsen I, Porter SR. Immunohistochemical and serological comparison of idiopathic and hepatitis C virus-associated forms of oral lichen planus. Eur J Oral Sci 1998;106:853-862.
- Koch P and Bahmer FA. Oral lesions and symptoms related to metals used in dental restorations: a clinical, allergological, and histologic study. J Am Acad Dermatol 1999;41:422-430.
- Lamey PJ, McCartan BE, MacDonald DG, MacKie RM. Basal cell cytoplasmic autoantibodies in oral lichenoid reactions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:44-49.
- Laurberg G, Geiger JM, Hjorth N, Holm P, Hou-Jensen K, Jacobsen KU et al. Treatment of lichen planus with acitretin. A double-blind, placebo-controlled study in 65 patients. J Am Acad Dermatol 1991;24:434-437.
- Lehner T, Lyne C. Adrenal function during topical oral corticosteroid treatment. Br Med J 1969;4:138-141.
- Ling MR. Topical tacrolimus and pimecrolimus: future directions. Semin Cutan Med Surg 2001;20:268-274.
- Lodi G, Carrozzo M, Hallett R, D'Amico E, Piattelli A, Teo CG et al. HCV genotypes in Italian patients with HCV-related oral lichen planus. J Oral Pathol Med 1997;26:381-384.
- Lodi G, Carrozzo M, Harris K, Piattelli A, Teo CG, Gandolfo S et al. Hepatitis C virus-associated oral lichen planus: no influence from hepatitis G virus co-infection. J Oral Pathol Med 2000;29:39-42.
- Lozada-Nur F, Miranda C. Oral lichen planus: epidemiology, clinical characteristics, and associated diseases. Semin Cutan Med Surg 1997a;16:273-277.
- Lozada-Nur F, Miranda C. Oral lichen planus: topical and systemic therapy. Semin Cutan Med Surg 1997b;16:295-300.
- Mahood JM. Familial lichen planus. A report of nine cases from four families with a brief review of the literature. Arch Dermatol 1983;119:292-294.
- Majorana A, Facchetti F, Pellegrini W, Sapelli P. Apoptosis-associated markers in oral lichen planus. J Oral Pathol Med 1999;28:47-48.
- McCartan BE, Lamey P. Lichen planus - specific antigen in oral lichen planus and oral lichenoid drug eruptions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;89:585-587.
- McCartan BE, McCreary CE. Oral lichenoid drug eruptions. Oral Dis 1997;3:58-63.
- Mignogna MD, Lo ML, Favia G, Mignogna RE, Carbone R, Bucci E. Oral lichen planus and HCV infection: a clinical evaluation of 263 cases. Int J Dermatol 1998;37:575-578.
- Mignogna MD, Lo ML, Lo RL, Fedele S, Ruoppo E, Bucci E. Oral lichen planus: different clinical features in HCV-positive and HCV-negative patients. Int J Dermatol 2000;39:134-139.
- Morrison L, Kratochvil FJ III, Gorman A. An open trial of topical tacrolimus for erosive oral lichen planus. J Am Acad Dermatol 2002;47:617-620.
- Nagao Y, Kameyama T, Sata M. Hepatitis C virus RNA detection in oral lichen planus tissue. Am J Gastroenterol 1998;93:850.
- Nagao Y, Sata M, Fukuizumi K, Ryu F, Ueno T. High incidence of oral lichen planus in an HCV hyperendemic area. Gastroenterology 2000a;119:882-883.
- Nagao Y, Sata M, Noguchi S, Seno'o T, Kinoshita M, Kameyama T et al. Detection of hepatitis C virus RNA in oral lichen planus and oral cancer tissues. J Oral Pathol Med 2000b;29:259-266.
- Nagao Y, Sata M, Suzuki H, Kameyama T, Ueno T. Histological improvement of oral Lichen planus in patients with chronic hepatitis C treated with interferon. Gastroenterology 1999;117:283-284.
- Okochi H, Nashiro K, Tsuchida T, Seki Y, Tamaki K. Lichen planus pemphigoides: case report and results of immunofluorescence and immunoelectron microscopic study. J Am Acad Dermatol 1990;22:626-631.
- Olivier V, Lacour JP, Mousnier A, Garraffo R, Monteil RA, Ortonne JP. Treatment of chronic erosive oral lichen planus with low concentrations of topical tacrolimus: an open prospective study. Arch Dermatol 2002;138:1335-1338.
- Ostman PO, Anneroth G, Skoglund A. Amalgam-associated oral lichenoid reactions. Clinical and histologic changes after removal of amalgam fillings. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:459-465.
- Plemons JM, Rees TD, Zachariah NY. Absorption of a topical steroid and evaluation of adrenal suppression in patients with erosive lichen planus. Oral Surg Oral Med Oral Pathol 1990;69:688-693.
- Porter SR, Kirby A, Olsen I, Barrett W. Immunologic aspects of dermal and oral lichen planus: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:358-366.
- Potts AJ, Hamburger J, Scully C. The medication of patients with oral lichen planus and the association of nonsteroidal anti-inflammatory drugs with erosive lesions. Oral Surg Oral Med Oral Pathol 1987;64:541-543.
- Regezi JA, Dekker NP, MacPhail LA, Lozada-Nur F, McCalmont TH. Vascular adhesion molecules in oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:682-690.
- Robertson WD, Wray D. Ingestion of medication among patients with oral keratoses including lichen planus. Oral Surg Oral Med Oral Pathol 1992;74:183-185.
- Rojo-Moreno JL, Bagan JV, Rojo-Moreno J, Donat JS, Milian MA, Jimenez Y. Psychological factors and oral lichen planus. A psychometric evaluation of 100 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:687-691.
- Roy KM, Dickson EM, Staines KS, Bagg J. Hepatitis C virus and oral lichen planus/lichenoid reactions: lack of evidence for an association. Clin Lab 2000;46:251-254.
- Rozycki TW, Rogers RS III, Pittelkow MR, McEvoy MT, el Azhary RA, Bruce AJ et al. Topical tacrolimus in the treatment of symptomatic oral lichen planus: a series of 13 patients. J Am Acad Dermatol 2002;46:27-34.
- Salem G. Oral lichen planus among 4277 patients from Gizan, Saudi Arabia. Community Dent Oral Epidemiol 1989;17:322-324.
- Schiodt M, Holmstrup P, Dabelsteen E, Ullman S. Deposits of immunoglobulins, complement, and fibrinogen in oral lupus erythematosus, lichen planus, and leukoplakia. Oral Surg Oral Med Oral Pathol 1981;51:603-608.
- Scully C, Porter SR. The clinical spectrum of desquamative gingivitis. In: Arndt K, LeBoit PE RJWB (eds). Seminars in Cutaneous Medicine and Surgery. WB Saunders 1997;308-313.
- Scully C, Beyli M, Ferreiro MC, Ficarra G, Gill Y, Griffiths M et al. Update on oral lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med 1998;9:86-122.
- Scully C, Eisen D, Carrozzo M. Management of oral lichen planus. Am J Clin Dermatol 2000;1:287-306.
- Silverman S Jr, Gorsky M, Lozada-Nur F. A prospective follow-up study of 570 patients with oral lichen planus: persistence, remission, and malignant association. Oral Surg Oral Med Oral Pathol 1985;60:30-34.
- Simark-Mattsson C, Bergenholtz G, Jontell M, Eklund C, Seymour GJ, Sugerman PB et al. Distribution of interleukin-2, -4, -10, tumour necrosis factor-alpha and transforming growth factor-beta mRNAs in oral lichen planus. Arch Oral Biol 1999;44:499-507.
- Sloberg K, Hersle K, Mobacken H, Thilander H. Topical tretinoin therapy and oral lichen planus. Arch Dermatol 1979;1156:716-718.
- Sugerman PB, Savage NW, Seymour GJ, Walsh LJ. Is there a role for tumor necrosis factor-alpha (TNF-alpha) in oral lichen planus? J Oral Pathol Med 1996;25:219-224.
- Tanda N, Mori S, Saito K, Ikawa K, Sakamoto S. Expression of apoptotic signaling proteins in leukoplakia and oral lichen planus: quantitative and topographical studies. J Oral Pathol Med 2000;29:385-393.
- Thorn JJ, Holmstrup P, Rindum J, Pindborg JJ. Course of various clinical forms of oral lichen planus. A prospective follow-up study of 611 patients. J Oral Pathol 1988;17:213-218.
- Toto PD, Nadimi HT. An immunohistochemical study of oral lichen planus. Oral Surg Oral Med Oral Pathol 1987;63:60-67.
- van der Meij EH, van der Waal I. Hepatitis C virus infection and oral lichen planus: a report from The Netherlands. J Oral Pathol Med 2000;29:255-258.
- van der Meij EH, van der Waal I. Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications. J Oral Pathol Med 2003;32:507-512.
- Varela P, Areias J, Mota F, Canelhas A, Sanches M. Oral lichen planus induced by interferon-alpha-N1 in a patient with hepatitis C. Int J Dermatol 2000;39:239-240.
- Vente C, Reich K, Rupprecht R, Neumann C. Erosive mucosal lichen planus: response to topical treatment with tacrolimus. Br J Dermatol 1999;140:338-342.
- 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.
- Voute AB, Schulten EA, Langendijk PN, Kostense PJ, van der Waal I. Fluocinonide in an adhesive base for treatment of oral lichen planus. A double-blind, placebo-controlled clinical study. Oral Surg Oral Med Oral Pathol 1993;75:181-185.
- Yiannias JA, el Azhary RA, Hand JH, Pakzad SY, Rogers RS III. Relevant contact sensitivities in patients with the diagnosis of oral lichen planus. J Am Acad Dermatol 2000;42:177-182.
Hospital General Universitario de Valencia, Valencia, Spain.
Dermatology Research Associates, Cincinnati, Ohio, USA.
International Centres for Excellence in Dentistry, and Eastman Dental Institute for Oral Health Care Sciences, University of London, London, UK.
Prof. Crispian Scully CBE, International Centres for Excellence in Dentistry, and Eastman Dental Institute for Oral Health Care Sciences, University of London, 256 Gray's Inn Road, London WC1X 8LD, UK, E-mail firstname.lastname@example.org