Oral Lichen Planus - Review - Ssdctumkur.org

Oral Lichen Planuscells in the subepithelial infiltrateexpress TNF in situ. 5,6Keratinocytes and lymphocytes incutaneous lichen planus expresselevated levels of the p55 TNFreceptor, TNF-RI. 7 T cells in orallichen planus contain mRNA forTNF and secrete TNF in vitro. 8Serum and salivary TNF levels areelevated in oral lichen planuspatients. 9,10,11,12TNFpolymorphisms have beenidentified in patients with orallichen planus, and they maycontribute to the development ofadditional cutaneous lesions. 13 Orallichen planus has been treatedsuccessfully with thalidomide, 14,15 ,while thalidomide is known tosuppress TNF production. 16,17Together, these data implicate TNFin the pathogenesis of oral lichenplanus.The lichen planus antigen isunknown, although it may be aself-peptide (or altered selfpeptide),in which case lichenplanus would be a trueVolume 2 Issue 1February 2011autoimmune disease. The role ofautoimmunity in the pathogenesisis supported by many autoimmunefeatures of oral lichen planus,including its chronicity, onset inadults, predilection for females,association with other autoimmunediseases, occasional tissue-typeassociations, depressed immunesuppressor activity in patients withoral lichen planus, and thepresence of autocytotoxic T-cellclones in lichen planus lesions. Theexpression or unmasking of thelichen planus antigen may beinduced by drugs (lichenoid drugreaction), contact allergens indental restorative materials ortoothpasteshypersensitivity(contactreaction),mechanical trauma (Koebnerphenomenon), viral infection, orother unidentified agents. 18,19,20FrequencyOral lichen planus affectsapproximately 1-2% of the generaladult population, although theprevalence of the disease is63 Journal of Dental Sciences and Research

Oral Lichen Planusunknown in many areas. 21 Orallichen planus is a commonnoninfectious oral mucosal disorderamong adult patients who attendoral pathology and oral medicineclinics.Mortality/Morbidity• Oral squamous cell carcinoma(SCC) developed in fewer than5% of patients with oral lichenplanus who did not use tobacco22,23,24Also see Cancers of theOral Mucosa.• Patients with atrophic(erythematous) or erosive(ulcerative) disease commonlyhave significant local morbidity.RaceOral lichen planus affects all racialgroups.SexThe female-to-male ratio for orallichen planus is 1.4:1.AgeOral lichen planus predominantlyoccurs in adults older than 40years, although younger adults andchildren can be affected.HistoryVolume 2 Issue 1February 2011The clinical history of oral lichenplanus and oral lichenoid lesionsvaries. Complete history taking andphysical examination by adermatologist may be required inpatients with extra-oral symptomsor signs associated with oral lichenplanus. 25Lichen planus may arise in patientswith other immunologicallymediated disorders, includingalopeciaareata, dermatomyositis,lichen sclerosis etatrophicus, morphea, myastheniagravis, primary biliarycirrhosis, ulcerativeand vitiligo.colitis,• In many patients, the onset oforal lichen planus is insidious,and patients are unaware oftheir oral condition. In suchinstances, the referring medicalor dental practitioner identifiesthe clinical changes in the oralmucosa.• Some patients report aroughness of the lining of the64 Journal of Dental Sciences and Research

Oral Lichen Planusmouth, sensitivity of the oralmucosa to hot or spicy foods ororal hygiene products, painfuloral mucosa, sore gums, red orwhite patches on the oralmucosa, red gums, or oralulcerations.• Approximately two thirds ofpatients with oral lichen planusreport oral discomfort, especiallyin association with atrophic anderosive lesions.o Erythematous and erosivelesions are often sensitive orpainful.o Symptoms vary from mucosalsensitivity to continuousdebilitating pain.• Oral mucosal lichenoid lesionsmay occur after theadministration of systemic drugssuch as nonsteroidal antiinflammatorydrugs (NSAIDs),sulfonylureas, antimalarials,beta-blockers, and someangiotensin-converting enzyme(ACE) inhibitors. The periodbetween the commencement ofVolume 2 Issue 1February 2011the drug therapy and the clinicalappearance of oral lichenplanus–like disease varies.• In rare cases, oral mucosallichenoid lesions occur after adental restoration is performedor after the patient starts using adenture; the lag period varies.Patients with an associatedallergy to metals or componentsof the appliance should beevaluated by means of patchtesting. 26• Up to 44% of patients with orallichen planus develop coincidentskin lesions. Conversely, morethat 70% of patients withcutaneous lichen planus developcoincident oral lichen planus.• The genitals are involved in asmany as 25% of women withoral lichen planus, comparedwith only 2-4% of men with orallichen planus.o The features are similar tothose of the oral lesions.o Patients do not often complainof pain or pruritus, although on65 Journal of Dental Sciences and Research

Oral Lichen Planusquestioning, they may admit tosuch symptoms.• In patients with oral lichenplanus, scalp involvement (lichenplanopilaris) is rare.• Nail involvement in patients withoral lichen planus is uncommon.• In a small group of patients,lichen planus may involve theesophagus.PhysicalPertinent physical findings in orallichen planus are limited to the oralmucosa. Some patients presentwith coincident lesions on the skin,scalp, nails, genital mucosa,esophageal mucosa, larynx, andconjunctivae. Complete historytaking and physical examination bya dermatologist may be required inpatients with extra-oral symptomsor signs associated with oral lichenplanus. 25Patients with reticular lesions areoften asymptomatic, whereasthose with atrophic (erythematous)or erosive (ulcerative) diseasecommonly have significant localVolume 2 Issue 1February 2011morbidity. The oral pain is variableand exacerbated by trauma andfoods, particularly those that arehot, spicy, or acidic.• Oral mucosal lesions are variableand present as white striations(Wickham striae), white papules,white plaques, erythema(mucosal atrophy), erosions(shallow ulcers), or blisters.o The lesions predominantlyaffect the buccal mucosa,tongue, and gingivae, althoughother oral sites are occasionallyinvolved.o The lesions are usuallybilateral.o The lesions may appear as amixture of clinical subtypes. Forexample, white streaks andgray streaks may form a linearor reticular pattern on anerythematousbackground.Alternatively, a central area ofshallow ulceration (erosion)may have a yellowish surface(fibrinous exudate) surroundedby an area of erythema.66 Journal of Dental Sciences and Research

Oral Lichen PlanusIn most patients, telltale whitestriations or papules areevident on the buccal mucosaor on the lateral margin of thetongue, either alone or incombination with other lesions.o Gingival lesions commonlyappear with a fiery rederythema that affects the entirewidth of the attached gingiva, acondition previously calleddesquamative gingivitis.o In patients predisposed topigmentation, oral lichen planuslesions may be associated withpatchy brown melanin depositsin the oral mucosa(inflammatory melanosis).• Oral lichen planus lesions usuallypersist for many years withperiods of exacerbation andquiescence.o During periods of exacerbation,the area of erythema or erosionincreases, with increased painand sensitivity.o During periods of quiescence,the area of erythema or erosionVolume 2 Issue 1February 2011decreases, with decreased painand sensitivity. Patients areoften unaware of quiescent orallichen planus, which maymanifest as faint whitestriations, papules, or plaques.o Exacerbations of oral lichenplanus have been linked toperiods of psychological stressand anxiety.• Lichenoid drug reactions havethe same clinical features asthose of idiopathic oral lichenplanus.o Lichenoid disease may beunilateral and associated withcirculating epithelial antinuclearantibodies, but few datasupport this possibility.o Rarely, lichenoid reactions ofthe oral mucosa occur on theoral mucosa in contact with (orclose to) an amalgam orcomposite resin dentalrestoration, or a denturecomponent.o Mechanical trauma (theKoebner phenomenon) may67 Journal of Dental Sciences and Research

Oral Lichen Planusexacerbate lichenoid lesions,especially when it affects themidline of the buccal mucosa orthe lateral margin of thetongue.• Up to 44% of patients with orallichen planus develop coincidentskin lesions. These typicallyappear as pruritic, flat-topped,violaceous papules and plaquesthat predominantly affect theflexor aspects of the wrists orankles, the extensor aspects ofthe lower legs, the skin of thelower central part of the back,and the natal cleft.• The genitals are involved in asmany as 25% of women withoral lichen planus, comparedwith only 2-4% of men with orallichen planus. The features aresimilar to those of oral lesions.• Nail involvement causes pitting,subungual hyperkeratosis,longitudinal melanonychia,onychorrhexis (longitudinalridging and grooving),Volume 2 Issue 1February 2011onychoschizia (distal splitting),and onycholysis (separation ofthe nail plate from the nail bed).Permanent damage to the nailmatrix results in the formation ofa pterygium (raised centralridge) and permanent nail loss(anonychia).• Scalp involvement (lichenplanopilaris) causes follicular andperifollicular violaceous scalypruritic papules, follicularplugging, bottlebrush hairformation (multiple hair shaftsemerging from a single follicularorifice), and atrophic scarringwith permanent patchy hair loss.• Rarely, laryngeal,esophageal,and conjunctival involvementoccur.CausesCurrent data suggest that orallichen planus is a T-cell–mediatedautoimmune disease in whichautocytotoxic CD8 +T cells triggerthe apoptosis of oral epithelialcells. However, the precise causeof oral lichen planus is unknown.68 Journal of Dental Sciences and Research

Oral Lichen PlanusVolume 2 Issue 1February 2011• The disease mechanism appears to involve several steps that could bedescribed as follows:Initiating factor/event{Antigenic stimulus: Exogenous/Endogenous}Focal release of regulatory cytokines{Langerhans cells & Factor XIIIa Dendrocytes}Upregulation of vascular adhesion molecules by endothelium{ICAM, ELAM, VCAM}Recruitment and retention of T lymphocytesCytotoxicity and apoptosis of basal keratinocytes{Mediated by T cells}Reduced keratinocyte desquamation and enhanced membraneadhesionHyperkeratosis{At the site of antigenic stimulus}LICHEN PLANUSReported associations between orallichen planus and systemicdiseases may be coincidental,because (1) oral lichen planus isrelatively common, (2) oral lichenplanus occurs predominantly inolder adults, and (3) many drugsused in the treatment of systemicdiseases trigger the developmentof oral lichenoid lesions as anadverse effect.In many patients, a cause for the69 Journal of Dental Sciences and Research

Oral Lichen Planusplanus and chronic hepaticdiseases such as hepatitis Cvirus (HCV) infection,autoimmune chronic activehepatitis, and primary biliarycirrhosis. 27,28o This association probablyreflects the geographicdistribution of HCV disease andlichenoid reactions to variousdrug therapies (eg, interferonalpha for HCV disease,penicillamine for primary biliarycirrhosis).o Oral lichen planus is associatedwith HCV infection and liverdisease in parts of Japan andsouthern Europe. Anassociation between oral lichenplanus and HCV infection hasnot been detected in British,French, German, Scandinavian,or American patients.• Oral lichenoid lesions may arisein people who habitually chewbetel quid. A causal role for betelquid in oral lichen planus has notbeen identified.Volume 2 Issue 1February 2011• Oral lichenoid lesions are part ofthe spectrum of chronic graftversus-hostdisease that occursafter allogeneic hemopoieticstem cell transplantation.• No consistent association withhuman leukocyte antigen (HLA)is reported in oral lichen planus.This finding suggests that thepatient's genetic backgrounddoes not play a critical role inoral lichen planus pathogenesis.• Exacerbations of oral lichenplanus have been linked toperiods of psychological stressand anxiety.• Little evidence supports aconnection between diabetesmellitus and oral lichen planus.The oral lichenoid lesion inGrinspan syndrome (triad of orallichen planus, diabetes mellitus,and hypertension) is probably anadverse effect of the drugtherapy for diabetes mellitus andhypertension.71 Journal of Dental Sciences and Research

Oral Lichen PlanusThe initial reaction whetherprogresses to the development ofOLP, or is switched off, probablydepends on a number of factorslike,i) The nature of the antigenii) The ability of the individual topresent the antigen (HLA type)iii) The presence of T cellscapable of recognizing theantigen (T cell receptorrepertoire)iv) Possibly the inheritance of aprofile of cytokine and othergene polymorphisms thatpromote, rather than suppress, acell-mediated response to theantigen.Differential diagnosisDermatitisHerpetiformisGraft Versus Host DiseaseLinear IgA DermatosisOral Manifestations of AutoimmuneBlisteringDiseasesPemphigusVulgarisSquamous Cell CarcinomaVolume 2 Issue 1February 2011Other Problems to BeConsideredLichenoid drug reactionLichenoid contact sensitivityreactionReactivekeratosisMucous membrane pemphigoidOral Crohn diseaseAnemicEpithelialstatesdysplasiaHepatitis C infectionChronic hepatic diseaseLaboratory Studies• The history, typical oral lesions,and skin involvement are usuallysufficient to diagnose oral lichenplanus (OLP), though laboratorystudies and biopsy may berequire.• Directimmunofluorescencetesting can help in distinguishingerosive or the rare bullous orallichen planus from pemphigusvulgaris, benign mucousmembranepemphigoid,dermatitis herpetiformis, andlinear immunoglobulin A (IgA)disease. However, oral lichen72 Journal of Dental Sciences and Research

Oral Lichen Planusplanus has no specific featuresat direct or indirectimmunofluorescence testing.• Some studies show an increasedincidence of C albicans infectionin patients with oral lichenplanus.o Periodic acid-Schiff (PAS)staining of biopsy specimensand candidal cultures or smearsmay be performed. However,these tests may be of limitedclinical value because oral Calbicans is present in more than70% of the population.o The presence of C albicans andthe oral load of this organismdo not aid either the diagnosisor the treatment of oral lichenplanus.Other Tests• Skin patch testing may behelpful in identifying a contactallergy in some patients with orallichen planus. 26o The current recommendation isto use a standard series; adental prosthesis series; and aVolume 2 Issue 1February 2011metal salt series that includesgold, mercury, and palladiumsalts as well as other salts ofmetals used in dentalrestorations.o Late readings, or thoseobtained at 10 and 17 daysafter the application of the skinpatch, may be required.o The most common allergy isrelated to mercury contained inamalgamrestorations.Compared with patients withlesions in other locations,patients with lesions near theamalgam restoration have ahigher rate of positive patchtest results to mercury. Whenthe amalgam restorations areremoved, patients with apositive result have a higherremission rates (47-100%depending on the study) thanthat of patients without thispositive result.• Although the assessment ofhepatic function in the treatmentof otherwise healthy southern73 Journal of Dental Sciences and Research

Oral Lichen PlanusEuropean and Japanese patientswith oral lichen planus may bewarranted, similar screening inBritish and American patientsappears to be of limited benefit.Formal studies are still ongoing.Consider hepatic biochemicaltesting only when patients haveproven oral lichen planus andsuspected liver disease.Procedures• Biopsy may be required toexclude malignancy or todifferentiate between oral lichenplanus and other white or chroniculcerative oral lesions, includingreactive keratoses, chronichyperplastic candidosis, epithelialdysplasia, discoid lupuserythematosus, gastrointestinaldisease (including oral Crohndisease), and anemic states.Histologic FindingsHistopathologic examination oflesional tissue is the most relevantinvestigation in cases of oral lichenplanus.Volume 2 Issue 1February 2011Consistent findings include abandlike subepithelial mononuclearinfiltrate consisting of T cells andhistiocytes, increased numbers ofintraepithelial T cells, anddegenerating basal keratinocytesthat form colloid (Civatte, hyaline,cytoid) bodies, which appear ashomogenous eosinophilic globules.Variable findings includeparakeratosis, acanthosis, andsawtooth rete pegs.Degeneration of the basalkeratinocytes and disruption of theanchoring elements of theepithelial basement membrane andbasal keratinocytes (eg,hemidesmosomes,filaments,fibrils) weakens the epithelialconnectivetissue interface. As aresult, histologic clefts (ie, Max-Joseph spaces) may form, andblisters on the oral mucosa(bullous lichen planus) may beseen at clinical examination. B cellsand plasma cells are uncommonfindings.Immunoglobulin or complement74 Journal of Dental Sciences and Research

Oral Lichen Planusdeposits are not a consistentfeature of oral lichen planus. Insome instances, fibrinogen andfibrin are deposited in a linearpattern in the basement membranezone. Colloid bodies contain fibrin,immunoglobulin M (IgM), C3, C4,and keratin. Laminin andfibronectin staining may be absentin areas of heavy fibrin depositionand colloid body formation. Thisfinding suggests basementmembrane damage in these areas.In oral lichen planus, electronmicroscopy is used principally as aresearch tool. The ultrastructure ofthe colloid bodies suggests thatthey are apoptotic keratinocytes,and recent studies using the endlabelingmethod revealed DNAfragmentation in these cells.Electron microscopy shows breaks,branches, and duplications of theepithelial basement membrane inoral lichen planus.TreatmentMedical treatment of oral lichenplanus (OLP) is essential for theVolume 2 Issue 1February 2011management of painful,erythematous, erosive, or bullouslesions. The principal aims ofcurrent oral lichen planus therapyare the resolution of painfulsymptoms, the resolution of oralmucosal lesions, the reduction ofthe risk of oral cancer, and themaintenance of good oral hygiene.In patients with recurrent painfuldisease, another goal is theprolongation of their symptom-freeintervals. 29,30,31The main concerns with the currenttherapies are the local andsystemic adverse effects and lesionrecurrence after treatment iswithdrawn. No treatment of orallichen planus is curative.• Eliminate local exacerbatingfactors.o Treat any sharp teeth or brokenrestorations or prostheses thatare likely to cause physicaltrauma to areas of erythema orerosion by using conventionaldental means. Scale the teethto remove calculous deposits75 Journal of Dental Sciences and Research

Oral Lichen Planusand reduce sharp edges.o If the patient has an isolatedplaquelike or erosive oral lichenplanus lesion on the buccal orlabial mucosa adjacent to adental restoration, and if anallergy is detected by means ofskin patch testing, the lesionmay heal if the offendingmaterial is removed orreplaced. (However, mostlichenoid lesions adjacent todental restorations areasymptomatic.)• If systemic drug therapy (eg,treatment with NSAIDs,antimalarials, or beta-blockers)is suspected as the cause of orallichenoid lesions, changing toanother drug may beworthwhile. This change must beundertaken only by the patient'sattending physician. However,the switch rarely resolves theerosions, and almost neverresolves the white patches oforal lichen planus.Volume 2 Issue 1February 2011• Inform all patients with orallichen planus about their slightlyincreased risk of oral SCC (themost common of all oralmalignancies).o As with all patients, advisethose with oral lichen planusthat this risk may be reducedby eliminating tobacco andalcohol consumption and byconsuming a diet rich in freshfruits and vegetables, amongother measure.o Erosive and atrophic lesions canbe converted into reticularlesions by using topicalsteroids. Therefore, theelimination of mucosalerythema and ulceration, with aresidual asymptomatic reticularor papular lesions, may beconsidered an end point ofcurrent oral lichen planustherapy. With respect to plaquelesions, the effect of treatmenton the risk of oral cancer isunclear.76 Journal of Dental Sciences and Research

Oral Lichen PlanusDiet• Patients with oral lichen planushave a slightly increased risk oforal SCC, although the preciserisk of oral cancer in patientswith oral lichen planus isunknown. Advise patients withoral lichen planus that a diet richin fresh fruit and vegetables mayhelp reduce the risk of oral SCC.• Advise patients with oral lichenplanus to do the following:o Eliminate smoking and alcoholconsumption.o Eat a nutritious diet, includingfresh fruit and vegetables,because this may help reducethe risk of oral cancer.o Pay attention when symptomsare exacerbated or whenlesions change.o Be aware of the need forregular re-examination andrepeat lesion biopsy, especiallyif clinical changes in the lesionoccur.• Although oral lichen planus doesnot increase the risk of dentalVolume 2 Issue 1February 2011caries or gingival disease, painfuloral lichen planus lesions(particularly those on the gums)can limit the patient's ability tomaintain good oral hygiene.Therefore, advise all patientswith oral lichen planus of theappropriate methods of oralhygiene and to see their dentistsoften.Topical corticosteroids are themainstay of medical treatment oforal lichen planus, although rarely,corticosteroids may beadministered intralesionally orsystemically. Some topicalcorticosteroid therapies maypredispose the patient to oralpseudomembranouscandidosis.However, this condition is rarely ifever symptomatic, and it generallydoes not complicate healing of theerosions related to oral lichenplanus. Topical antimycotics (eg,nystatin, amphotericin) may beprescribed either empirically ifconcern about candidal infection77 Journal of Dental Sciences and Research

Oral Lichen PlanusVolume 2 Issue 1February 2011To summarize, an empirical suggested line of treatment from variousevidence based studies can be as followsOLP DiagnosisHistoryDrugsClinical assessmentHistology, direct immunofluorescenceHCV testPatch test for dental materialsAsymptomatic.Improve / control oral hygiene,Avoid precipitating factors: drugs, food,chemicals, dental materialsReassurance.Erosive & / orSymptomatic.No treatmentReassurance onlyPositiveSmear for CandidaFollow up every 6monthsNegativeMild symptomsSevere symptomsMild symptomsSevere symptomsTopical steroids +AntifungalsBurst systemic+Topical steroids +AntifungalsTopical steroidsBurst systemic +Topical steroidsSatisfactoryresponseUnsatisfactoryresponseSatisfactoryresponseUnsatisfactoryresponseMaintenance withtopical steroidAlternativetreatmentsIntralesionalsteroidsFollow UpMaintenance withtopical steroidUnsatisfactoryresponseFollow UpAlternativetreatments80 Journal of Dental Sciences and Research

Oral Lichen PlanusComplications• Oral lichen planus and itstreatment may predisposepeople to oral C albicanssuperinfection.• Patients with oral lichen planusmay have a slightly increasedrisk of oral cancer, which theymay be able to reduce (seeDeterrence/Prevention).• Oral SCC in patients with orallichen planus is a fearedcomplication and a controversialissue.o In retrospective studies, fewerthan 5% of patients with orallichen planus who were notusing tobacco productsdeveloped oral SCC.o Atrophic, erosive, and plaquelesions may be at greater riskof malignant change, althoughSCC may arise in theunaffected oral mucosa as well.o The most important risk factorsof oral SCC remain theconcomitant use of alcohol andtobacco products. Any additiveVolume 2 Issue 1February 2011effect of oral lichen planus isdifficult to detect in patientswho use both.• Proposed reasons for theincreased risk of oral SCC inpatients with oral lichen planusinclude the following:o Compared with healthymucosa, the oral mucosaaffected by oral lichen planusmay be more sensitive to Calbicans and to the exogenousmutagens found in tobacco,alcohol, and betel quid.o In patients with oral lichenplanus, the chronicinflammatory response and thesimultaneous healing responseof epithelial wounds mayincrease the likelihood ofcancer-forming gene mutations.Prognosis• Oral lichen planus is a chronicinflammatory disease.o The lesions of cutaneous lichenplanus typically resolve within1-2 years, whereas the lesions81 Journal of Dental Sciences and Research

Oral Lichen Planusof oral lichen planus are longlasting and persist for 20 yearsor longer.o Resolution of the whitestriations, plaques, or papulesis rare.o Symptomatic oral lichen planus(ie, atrophic or erosive disease)characteristically waxes andwanes, although the associatedwhite patches do not resolve.• Current immunosuppressivetherapies usually control oralmucosal erythema, ulceration,and symptoms in patients withoral lichen planus with minimaladverse effects. However, arange of therapies may need tobe tried.• Advise patients that oral lichenplanus lesions may persist formany years with periods ofexacerbation and quiescence.• Follow up patients with orallichen planus at least every 6months for clinical examinationand repeat biopsy as required,although patients should beVolume 2 Issue 1February 2011advised to seek medical carewhenever the symptoms areexacerbated or the presentationof the lesions change.• In the context of appropriatemedical care, the prognosis formost patients with oral lichenplanus is excellent.Patient Education• Patient education is important.Many patients with oral lichenplanus are concerned about thepossibilities of its malignancyand contagiousness. Manypatients are frustrated by thelack of available patienteducation concerning oral lichenplanus. 33• Inform patients with oral lichenplanus of the following:o The chronicity of oral lichenplanus and the expectedperiods of exacerbation andquiescenceo The aims of treatment,specifically the elimination ofmucosal erythema, ulceration,pain, and sensitivity82 Journal of Dental Sciences and Research

Oral Lichen Planuso The lack of large randomizedcontrolled therapeutic clinicaltrialso The possibility that severaltreatments may need to betriedo The potentially increased risk oforal cancero The possibility of reducing therisk of oral cancer .References1. Sugerman PB, Satterwhite K,Bigby M. Autocytotoxic T-cellclones in lichen planus. Br JDermatol. Mar 2000;142(3):449-56.2. Sugerman PB, Savage NW,Walsh LJ, et al. Thepathogenesis of oral lichenplanus. Crit Rev Oral BiolMed. 2002;13(4):350-65.3. Younes F, Quartey EL,Kiguwa S, PartridgeM. Expression of TNF and the55-kDa TNF receptor inepidermis, oral mucosa,lichen planus and squamouscellVolume 2 Issue 1February 2011carcinoma. OralDis. Mar 1996;2(1):25-31.4. Sklavounou A, Chrysomali E,Scorilas A, Karameris A. TNFalphaexpression andapoptosis-regulating proteinsin oral lichen planus: acomparativeimmunohistochemicalevaluation. J Oral PatholMed. Sep 2000;29(8):370-5.5. Khan A, Farah CS, SavageNW, Walsh LJ, Harbrow DJ,Sugerman PB. Th1 cytokinesin oral lichen planus. J OralPatholMed. Feb 2003;32(2):77-83.6. Thongprasom K, DhanuthaiK, Sarideechaigul W,Chaiyarit P, ChaimusigM. Expression of TNF-alphain oral lichen planus treatedwith fluocinolone acetonide0.1%. J Oral PatholMed. Mar 2006;35(3):161-6. .83 Journal of Dental Sciences and Research

Oral Lichen Planus7. Simon M Jr, GruschwitzMS. In situ expression andserum levels of tumournecrosis factor alphareceptors in patients withlichen planus. Acta DermVenereol. May 1997;77(3):191-3.8. Simark-Mattsson C,Bergenholtz G, Jontell M, etal. Distribution of interleukin-2, -4, -10, tumour necrosisfactor-alphaandtransforming growth factorbetamRNAs in oral lichenplanus. ArchOralBiol. Jun 1999;44(6):499-507.9. Karagouni EE, Dotsika EN,Sklavounou A. Alteration inperipheralbloodmononuclear cell functionand serum cytokines in orallichen planus. J Oral PatholMed. Jan 1994;23(1):28-35.10. Sugermann PB, SavageNW, Seymour GJ, WalshLJ. Is there a role for tumorVolume 2 Issue 1February 2011necrosis factor-alpha (TNFalpha)in oral lichenplanus?. J Oral PatholMed. May 1996;25(5):219-24. .11. Sklavounou A, etal. Elevated serum levels ofthe apoptosis relatedmoleculesTNF-alpha,Fas/Apo-1 and Bcl-2 in orallichen planus. J Oral PatholMed. 2004;33:386-390.12. Rhodus NL, Cheng B,Myers S, Bowles W, Ho V,Ondrey F. A comparison ofthe pro-inflammatory, NFkappaB-dependentcytokines: TNF-alpha, IL-1-alpha, IL-6, and IL-8 indifferent oral fluids from orallichen planus patients. ClinImmunol. Mar 2005;114(3):278-83.13. Carrozzo M, Uboldi deCapei M, Dametto E, etal. Tumor necrosis factoralphaand interferon-gammapolymorphisms contribute to84 Journal of Dental Sciences and Research

Oral Lichen Planussusceptibility to oral lichenplanus. JInvestDermatol. Jan 2004;122(1):87-94.14. Dereure O, Basset-Seguin N, Guilhou JJ. Erosivelichen planus: dramaticresponsetothalidomide. ArchDermatol. Nov 1996;132(11):1392-3.15. Camisa C, PopovskyJL. Effective treatment of oralerosive lichen planus withthalidomide. ArchDermatol. Dec 2000;136(12):1442-3.16. Sampaio EP, Sarno EN,Galilly R, Cohn ZA, KaplanG. Thalidomide selectivelyinhibits tumor necrosis factoralpha production bystimulatedhumanmonocytes. J Exp Med. Mar1 1991;173(3):699-703.17. Moreira AL, SampaioEP, Zmuidzinas A, Frindt P,Smith KA, KaplanVolume 2 Issue 1February 2011G. Thalidomide exerts itsinhibitory action on tumornecrosis factor alpha byenhancingmRNAdegradation. J Exp Med. Jun1 1993;177(6):1675-80.18. Porter SR, Kirby A,Olsen I, BarrettW. Immunologic aspects ofdermal and oral lichenplanus: a review. Oral SurgOral Med Oral Pathol OralRadiolEndod. Mar 1997;83(3):358-66.19. Scully C, Beyli M,Ferreiro MC, et al. Update onoral lichen planus:etiopathogenesisandmanagement. Crit Rev OralBiol Med. 1998;9(1):86-122.20. Sugerman PB, SavageNW, Zhou X, Walsh LJ, BigbyM. Oral lichen planus. ClinDermatol. Sep-Oct 2000;18(5):533-9.85 Journal of Dental Sciences and Research

Oral Lichen Planus21. Axéll T, RundquistL. Oral lichen planus--ademographicstudy. Community Dent OralEpidemiol. Feb 1987;15(1):52-6.22. Eisen D. The clinicalfeatures, malignant potential,and systemic associations oforal lichen planus: a study of723 patients. J Am AcadDermatol. Feb 2002;46(2):207-14.23. Eisenberg E. Oral lichenplanus: a benign lesion. JOralMaxillofacSurg. Nov 2000;58(11):1278-85.24. Silverman S Jr. Orallichen planus: a potentiallypremalignant lesion. J OralMaxillofacSurg. Nov 2000;58(11):1286-8.25. Eisen D. The evaluationof cutaneous, genital, scalp,nail, esophageal, and ocularinvolvement in patients withVolume 2 Issue 1February 2011oral lichen planus. Oral SurgOral Med Oral Pathol OralRadiolEndod. Oct 1999;88(4):431-6.26. Koch P, BahmerFA. Oral lesions andsymptoms related to metalsused in dental restorations: aclinical, allergological, andhistologic study. J Am AcadDermatol. Sep 1999;41(3 Pt1):422-30.27. Lodi G, Porter SR,Scully C. Hepatitis C virusinfection: Review andimplications for thedentist. Oral Surg Oral MedOral Pathol Oral RadiolEndod. Jul 1998;86(1):8-22.28. Lodi G, Scully C,Carrozzo M, Griffiths M,Sugerman PB, ThongprasomK. Current controversies inoral lichen planus: report ofan internationalconsensusmeeting. Part 1. Viralinfectionsand86 Journal of Dental Sciences and Research

Oral Lichen Planusetiopathogenesis. Oral SurgOral Med Oral Pathol OralRadiolEndod. Jul 2005;100(1):40-51.29. Chan ES, Thornhill M,Zakrzewska J. Interventionsfor treating oral lichenplanus. Cochrane DatabaseSyst Rev. 2000;CD001168.30. Eisen D. The therapy oforal lichen planus. Crit RevOralBiolMed. 1993;4(2):141-58.31. McCartan B, McCrearyC. What is the rationale fortreating oral lichenplanus?. OralDis. Jul 1999;5(3):181-2.Volume 2 Issue 1February 201132. [Guideline] Referralguidelines for suspectedcancer in adults andchildren. NationalCollaborating Centre forPrimary Care, Royal CollegeofPractitioners. NationalGuidelineClearinghouse. Jun 2005.General33. Burkhart NW, BurkesEJ, Burker EJ. Meeting theeducational needs of patientswith oral lichen planus. GenDent. Mar-Apr 1997;45(2):126-32; quiz143-4.87 Journal of Dental Sciences and Research