CLINICAL IPDATE ON = ORAL LICHEN PLANUS

CLINICAL UPDATE ON ORAL = LICHEN=20 PLANUS

SPECIALITY &nbs= p; =20 : =20 Dental (Oral Medicine and Radiology)

CME &nbs= p; =20 &nbs= p; =20 : =20 On Clinical update on Oral Lichen Planus

NAME OF THE EXPERT : =20 Dr.S.JAYACHANDRAN, M.D.S.,

&nbs= p; = ; = &= nbsp; =20 Professor and Head of Department,

&nbs= p; = ; = &= nbsp; =20 Department of Oral Medicine and Radiology,

Tamil Nadu Govt.=20 Dental College and Hospital,

Chennai =96 600=20 003.

ABSTRACT &nbs= p;=20 :

Oral Lichen Planus = is a=20 chronic mucosal condition commonly encountered in clinical dental = practice with=20 the prevalence of 0.1 to 4%. It has various oral manifestations, the = reticular=20 form being the most common. Despite recent advances in understanding the = immunopathogenesis of Oral Lichen Planus, the initial triggers of lesion = formation and the essential pathogenic pathways are unknown. It is = therefore not=20 surprising that the clinical management of Oral Lichen Planus poses = considerable=20 difficulties to the Dermatologist and the Oral Physician. This paper = focuses on=20 the clinical features, histopathology, patient management and treatment=20 approaches of Oral Lichen Planus.

=20 Lichen planus=20 is a chronic inflammatory mucocutaneous disease which can affect the = stratified=20 squamous epithelium of the skin, oral mucosa and genitilia, of uncertain = aetiology but of somewhat unique histopathological=20 features.

=20 The classical appearance of LP, of white papules on the buccal = and=20 lingual mucosa was recognized by Wilson and Thibierge and it was soon=20 appreciated that ulcerative and bullous form of LP=20 existed.

PREVALENCE=20 :

The = prevalence=20 of oral lichen planus in the general population is of the order of 0.1 = to=20 4%.

AGE=20 :

=20 LP predominantly is a disease of the middle aged and elderly with = ages=20 ranging from 30 =96 70 years. Children occasionally are affected and LP = has ever=20 been described in an infant under the age of 6 = months.

SEX :=20

=20 LP afflicts both sexes but, the vast majority from several = different=20 countries, have revealed that some 60 to 65% of patients are=20 female.

GEOGRAPHICAL:

=20 LP has been recorded in patients of all = races.

SITES=20 :

=20 LP may involve the skin and appendages, oral mucosa and other = mucous=20 membranes in any combination.

ETIOLOGY AND=20 PATHOGENESIS :

=20 LP is not a classical autoimmune disorder. Autoantibodies are = uncommonly=20 detected in LP; anti nuclear antibodies are developed in low titre.=20 Hypergammaglobulinemia is not a consistent feature of LP and it has no=20 consistent association with any of the classical autoimmune disorders.=20 Furthermore, there is no correlation between the presence of immune = deposits and=20 the clinical pattern of disease. Bacterial, viral and fungal causes have = proved=20 negative.

HYPOTHESIS=20 FOR THE IMMUNOPATHOGENESIS OF ORAL LP:

=20 Antigen presenting cells (APCs) and basal keratinocytes are = activated by=20 antigenic stimulations (exo or endogenous). Activated antigen presenting = cells=20 and keratinocytes secrete chemokines that attract the lymphocytes into = the=20 developing oral LP lesion.

=20 Activated antigen presenting cells present antigen associated = with MHC=20 class II to CD4⁺ T cells (2a). Activated basal keratinocytes = present=20 antigen associated with MHC class I to CD8⁺ T cells (2b). = CD40 and=20 CD80 co expression and IL =96 2 and IFN =96 gamma (3a) which bind their = respective=20 receptors on CD8⁺ T cells (3b). Activated antigen =96 = specific=20 CD8⁺ cytotoxic T cells expressed FasL or secrete granzyme B = or TNF -=20 a that trigger basal keratinocytes apoptosis=20 (5).

OTHER=20 POSSIBLE ETIOLOGICAL FACTORS :

1. Drugs and=20 Chemicals : The occurrence of = lesions=20 having the clinical and histopathological features of LP, but apparently = induced=20 by drugs, has been recognized. A vast range of drugs have been = implicated such=20 as antidiabetics, antihypertensives, antimalarials, antirheumatic drugs = and also=20 hepatitis B vaccine. Drug induced lichenoid lesions should be identified = where=20 possible, because potentially they are reversible. Contact allergy to = copper in=20 dental alloys or mercury has been suggested as a cause of LP or oral = lichenoid=20 lesions. In susceptible individuals, amalgam fillings may induce amalgam = =96=20 contact hypersensitivity lesions with features similar to OLP. Such = lesions are=20 likely to occur on mucosal surfaces in intimate contact with amalgam = fillings=20 and could be expected to improve following removal of the=20 fillings.

2.=20 Infections: Among the exogenous factors, several = infective=20 agents including some viruses and H.pylori have recently been linked = with oral=20 LP. DNA from HSV =96 1, CMV and HHV =96 6 has occasionally been found = with the OLP=20 tissue, mainly in erosive lesions. Lichenoid lesions have been reported = in=20 patients with HIV infection, but most of them could be related to = zidovudine or=20 ketaconazole therapy. The frequent association of LP with chronic liver = disease=20 is well documented. Nevertheless, most patients with LP and chronic = liver=20 disease are not HBV =96 infected. The association of LP with primary = biliary=20 cirrhosis is mostly due to the administration of penicillamine = treatment. HCV =96=20 associated hepatic disease may precede LP onset or may be diagnosed = together=20 with it. To date, 36 studies have analysed the prevalence of HCV = infection among=20 LP patients. It is suggested that HCV =96 specific T cells may play a = role in the=20 pathogenesis of oral LP ; oral cell damage being the possible result of = a direct=20 immune aggression of epithelial cells expressing HCV antigens, possibly=20 sustained by a cytokine environmental favourable to trigger and maintain = the=20 lichenoid reactions.

3.=20 Psychogenic factors : The = supposed=20 association of LP with hysteria, anxiety or depression has not been = confirmed.=20 Further more, there is no apparent association with social class or=20 occupation.

4. Habits=20 : Smoking may have some influence on the = disease. In=20 contrast, chewers of tobacco or of tobacco and betal, have increased = prevalence=20 of oral LP.

5.=20 Miscellaneous factors : Suggested=20 association of LP with deficiencies of B1, B6 and C and electric = potentials=20 require further study.

CLINICAL=20 TYPES :

=20 The oral lesions of LP appear to be more pleomorphic. Upto 6 = clinical=20 appearances have been described and several may be present in any = individual=20 patient.

1. Reticular=20 : It is the most common type. It = consists of=20 slightly raised fine whitish lines in an interlocking lace like pattern=20 (=93Honiton lace=94 of =91Wickham=92s striae=94) or in an annular = arrangement. It affects=20 the buccal mucosa predominantly.

2. Papular:=20 Small (0.5 to 1mm) white = raised papules=20 may be seen. They sometimes coalesce.

3. Plaque =96=20 Like: White plaques closely = resemble=20 leukoplakia but perhaps with a reticular surround may be seen. Involves=20 primarily the tongue dorsum and the buccal mucosa.

4. Atrophic:=20 Atrophic LP presents as = diffuse red or=20 erythroplakic lesion with peripheral white striae. On many occasions = keratotic=20 element is absent. Attached gingiva is frequently=20 involved.

5.=20 Erosive: Erosions are often extensive, irregular and = affect=20 mainly the lingual and buccal mucosa and are often associated with white = lesions. Gingival involvement in erosive LP produces desquamative = gingivitis. It=20 may closely resemble those of pemphigus, pemphigoid or lupus=20 erythematosus.

6.Bullous:=20 Bullous LP is rare. Bullae = are short=20 lived which rupture leaving an ulcerated, extremely uncomfortable = surface. =20 The reticular and atrophic forms were by far the most = common. Patients with oral LP often = are=20 asymptomatic.

SITE=20 DISTRIBUTION : = OLP almost invariably is a bilateral disease. = Oral=20 lesions usually involve the posterior buccal mucosa or less commonly the = tongue=20 and although any site can be involved palatal and sublingual lesions are = very=20 uncommon.

NATURAL=20 HISTORY : = Oral LP appears to have a quite different = natural=20 history, pursuing a far more chronic course.

MALIGNANT=20 POTENTIAL : = The frequency of oral cancer among oral LP = patients=20 reported in 3 of the 4 retrospective studies available from 1985 to the = present=20 was ≤ 1/5%, with the follow =96 up from 4.5 to 7.5 years. = Atrophic, erosive and=20 plaque lesions may be at a greater risk.

CUTANEOUS LICHEN = PLANUS=20 : = Cutaneous=20 LP may precede or follow involvement of the other tissues, = characterized, by a=20 flat topped, polygonal, violaceous pruritic papule about 2 =96 4 mm in = diameter=20 and may have whitish striae on the surface. It affects predominantly the = lumbar=20 region, genitilia, flexor surface of the wrists and the anterior surface = of the=20 lower legs. Trauma may induce the development of an isomorphous reaction = with KOEBNER PHENOMENON. The = natural history=20 of cutaneous LP is spontaneous resolution with 89% clearing within 2 = years=20 leaving some melasmic staining.

WORK =96 UP : = Lichenoid lesions = which=20 should be excluded include

- =20 Drug induced=20 lesions

- =20 Dental materials = induced=20 lesions

- =20 Graft =96 versus = =96 host=20 disease

- =20 Hepatic disease / = HCV=20 infection

Skin testing for = hypersensitivity to=20 drugs / dental materials is only rarely of clinical = value.

LAB STUDIES=20 :

1. =20 HISTOPATHOLOGY=20 :

The classical histopathological features of LP = include

- =20 Hyperorthokeratosis or=20 hyperparakeratosis

- =20 Acanthosis

- =20 Thickening of = the granular=20 cell layer

- =20 Basal cell = liquefaction=20

- =20 Saw tooth = configuration of=20 rete ridges

- =20 Band like dense=20 inflammatory cellular infiltrate in the upper lamina=20 propria

- =20 Colloid bodies = (civatte,=20 cytoid bodies) are seen in the epithelial malphigian layer and lamina = propria=20 resulting from fibrillar transformation, degeneration and premature cell = death=20 of basal keratinocytes. If the necrotic material is extruded into the = lamina=20 propria, the material may be taken up by phagocytes or provide a=20 matrix.

Hyperkeratosis is more common in oral than = cutaneous LP,=20 but the retepegs rarely are =93Saw tooth=94 in oral LP. The infiltrate = is=20 predominatly of T lymphocytes but there is no correlation of infiltrate = with the=20 clinical type of LP.

2. = DIRECT=20 IMMUNOFLUORESCENT TESTING :

= =20 Direct immunofluorescence demonstrates a shaggy band of = fibrinogen in the=20 basement membrane zone in 90 =96 100% of cases. Patients also may have = multiple=20 mainly IgM - staining cytoid bodies, usually located in the dermal = papilla or in=20 the peribasilar area. The cytoid bodies are considered to be highly = suggestive=20 of lichen planus if they are present in large numbers or grouped in = clusters.=20

When clinical findings cannot confirm the = diagnosis=20 satisfactorily, the use of histopathologic evaluation and direct=20 immunofluorescence is of great importance. The fibrinogen deposition in = oral LP=20 lesions seemed to be associated with an inflammatory process that = damaged the=20 connective tissue epithelial junction.

3. = OTHER TESTS=20 :

=B7 =20 Increased = incidence of=20 C.albicans infections in patients with oral lichen = planus.

=20 - PAS staining of biopsy specimens

=20 - Candidal cultures

=B7 =20 Assessment of = hepatic=20 function

=B7 =20 Hepatic = biochemical=20 testing

MANAGEMENT :=20

The elimination of mucosal erythema and = ulceration with=20 a residual asymptomatic reticular or papular lesions may be considered = an end=20 point of current oral lichen planus therapy

MEDICAL CARE=20 : =20 Reassuring the patient is very important. Patients with = symptomatic oral=20 LP often require therapy and should be treated if symptoms are=20 significant.

=20 As oral LP is a chronic disease, the patient=92s medical history, = psychological state and treatment compliance as well as possible drug=20 interaction, must be considered when evaluating the cost effectiveness = of any=20 treatment modalities. = When oral=20 lichenoid lesions are suspected to be related to the use of a given = drug, the=20 physician should be consulted as to the possible changes in=20 therapy.

=20 Plaque and calculus deposits are associated with a significantly = higher=20 incidence of erythematous and erosive gingival oral LP lesions, whereas = good=20 oral hygiene is essential and can enhance healing. Mechanical trauma of = dental=20 procedures, friction from sharp cusps, rough dental restoration and = poorly=20 fitting dental prosthesis can be exacerbating factors of symptomatic = oral LP and=20 should receive attention.

=20 Dental amalgam can cause oral lichenoid lesions which may improve = following, replacement of amalgam with other restorative materials. = Especially=20 in patients with positive patch test to mercury compounds. Even = composite resin=20 restoration can occasionally induce lichenoid = lesions.

Studies have reported that stress is one of = the most=20 frequent causes of acute exacerbation in oral LP patients. Associated = disorders=20 such as diabetes mellitus or hepatitis C virus infection should be = treated by=20 physician. Alcohol and tobacco consumption should be reduced. Intake of = fresh=20 fruits and vegetables is advocated.

DRUG THERAPY=20 : Since none of the available = treatment=20 is specific or universally successful and may have adverse effects, = active=20 therapy is largely reserved for erosive and ulcerative OLP or non =96 = erosive=20 symptomatic lesions.

1.=20 CORTICOSTEROIDS :

Topical=20 corticosteroids :

=20 They are widely used in the treatment of oral LP to reduce pain = and=20 inflammation

Hydrocortisone hemisuccinate pellets or in = aqueous=20 solutions are often of little benefit in OLP=20
Betamethasone showed some=20 effectiveness

=B7 =20 Decreases = inflammation by=20 suppressing PMNs migration and reversing increased capillary=20 permeability

=B7 =20 Affects = production of=20 lymphokines

=B7 =20 Inhibitory = effect on=20 Langerhans cells

=B7 =20 Adult dose : 0.5 = mg tab in=20 10 to 15ml water =96 mouth rinse for

1 min tid / qid until erythema / erosion=20 resolves.

=B7 =20 Interactions : = Effects=20 decrease with co =96 use of Phenytoin, Rifampin and Barbiturates. = Decreases the=20 effect of salicylates and immunization vaccines.

Disodium betamethasone phosphate mouthwashes = can be used=20 in widespread oral LP but, it may cause a significant systemic = absorption=20 leading to a pituitary =96 adrenal axis = suppression.

Flucinolone is a medium potency steroid. = Inhibits cell=20 proliferation. It has immunosuppressive, antiproliferative and=20 anti-inflammatory action. Adult dose :

0.1% cream / gel / ointment with or without = orabase.=20 Apply thin layer to surface tid / qid until they = resolve.

Triamcinolone is a medium potency steroid = similar to=20 flucinolone. 0.1% triamcinolone acetonide in orabase qid can be = applied as a=20 thin layer to surface until they resolve.

Fluocinolone acetonide 0.1% in orabase has = been shown to=20 be more effective than a similar triamcinolone acetonide 0.1% = preparation with=20 no serious side effects.

Clobetasol is a high potency class I = superpotent=20 steroid. It suppresses mitosis and increases synthesis of proteins = that=20 decreases inflammation and cause vasoconstriction. =

Adult dose : 0.05% of gel / cream / ointment. = Clobetasol=20 can be more effective than fluocinonide in improving lesions and the = long =96 term=20 use of clobetasol may help to control the disease.

The topical forms are applied daily to meet = each=20 patients needs. Topical steroids can be applied to the lesions with = cotton swabs=20 or with gauze pads impregnated with steroid. Extensive erosive lesions = of OLP on=20 the gingiva may be treated effectively by using occlusal splints as = carriers for=20 topical steroids.

Beclomethasone can be used with metered dose = inhaler=20 with 50mcg per puff upto 8 puffs/day.

Documented hypersensitivity, microbial = infections=20 contraindicate the use of corticosteroids. Prolonged use over large = denuded=20 areas with occlusive dressing and potent steroids lead to cushing=92s = syndrome,=20 reversible HPA =96 axis suppression, hyperglycemia or glycosuria. = Cautious use is=20 recommended in diabetes mellitus and hypertension. =

Intralesional=20 Corticosteroids : = Intralesional injections of hydrocortisone,=20 dexamethasone, triamcinolone acetonide and methylpredinisolone have been = used in=20 the treatment of oral LP. The injections can be painful, are not = invariably=20 effective and have a localized effect such as mucosal=20 atrophy.

Systemic=20 Corticosteroids : They are = probably the=20 most effective treatment for patients with diffuse erosive oral LP or = multisite=20 disease. This may be indicated in patients whose conditions is = unresponsive to=20 topical steroids.

Prednisolone decreases inflammation by = suppressing PMN=20 migration and by reducing capillary permeability. =

Adult dose=20 : 0.5 =96 2mg / kg / day = per orally /=20 i.m. / i.v. Slowly taper as the condition resolves. Single morning dose = is safer=20 for long term use. Discontinue if no response within 3=20 weeks.

Interactions : Co =96 use with estrogen may = decrease=20 clearance. Concurrent = digoxin cause=20 digitalis toxicity secondary to hypokalemia. Phenobarbitome, phenytoin = and=20 rifampin may increase metabolism of glucocorticoid. So consider = increasing the=20 maintenance dose. Co =96 use with diuretics =96 monitor for=20 hypokalemia

Topical treatments can be used with systemic=20 corticosteroids to reduce the systemic side effects or can be used=20 alone.

2.=20 IMMUNOSUPPRESSIVE AGENTS :

=20 Used for painful, = erythematous=20 or erosive OLP that are recalcitrant to = corticosteroids.

AZATHIOPRINE=20 :

=20 Successful steroid sparing adjunct to systemic prednisone therapy = and as=20 monotherapy may provide an alternative choice, if there are risk factors = against=20 steroid use.

It antagonizes purine metabolism =
Inhibits synthesis of DNA, RNA and proteins=20
Decrease proliferation of immune cells =96 = lower=20 autoimmune activity. =20

Adult dose :=20 1mg/ kg/ day (75 =96 150 = mg/day)=20 perorally for 6 =96 8 weeks. It may induce bone marrow suppression = especially in=20 heterozygotes for high activity of the enzyme TPMT. (Thiopurine Methyl=20 Transferase).

=B7 =20 Increase dose by = 0.5mg /=20 kg every 4 week until response or dose reaches 2.5mg/kg if serum TPMT = level >=20 19U.

=B7 =20 Increase by 1.5 = mg/ kg / d=20 if TPMT is 13.7 =96 19U

=B7 =20 Increase by 0.5 = mg/ kg / d=20 is TPMT is 5 =96 1.36 U

Maintenance=20 Dose : 1 - 2 mg / kg / day per orally or=20 i.v.

Contraindication : Documented hypersensitivity, Low levels = (<5) of serum=20 TPMT, Lesch Nyhan syndrome =96 lack of activating enzyme HGPRT =96 No = response to=20 this drug.

Interactions :=20 Toxicity increases with allopurinol or low levels of TPMT. Concurrent = ACE=20 inhibitors may produce : Severe leucopenia, increases level of = methotrexate=20 metabolites, decreases effects of anticoagulants, neuromuscular blockers = and=20 cyclosporine.

Unsafe In=20 Pregnancy

Precautions=20 : Reduce dose in renal insufficiency. Cause GIT disturbances. = Increased risk=20 of neoplasia and infection. Caution in liver disease. Hematologic = toxicities can=20 occur. Rarely associated with hypersensitivity reaction or pancreatitis. = Check=20 TPMT levels prior to therapy and monitor liver, renal and hematologic=20 function.

CYCLOSPORINE:

=20 It is a polypeptide that inhibits the transcription of several = cytokine=20 genes, thereby suppressing T =96 cell cytokine = production

=B7 =20 It is a non =96 = myelotoxic=20 immunosuppressant.

=B7 =20 The adverse side = effects=20 (importantly renal dysfunction) and the chronicity of oral lesions have=20 dissuaded the systemic use.

=B7 =20 Mouth rinses = (450 =96 1500=20 mg d^-1 for 8 =96 12 weeks)

=B7 =20 Finger = application of base=20 solution (100mg d^-1 for 4 weeks)

=B7 =20 Cellulose base = preparation=20 (48 mg d^-1 for 8 weeks) produce significant improvement in = OLP, with=20 no reliable side effects and little systemic = absorption.

Side effects=20 : Bad taste, Transient = burning=20 sensation on initial application, High cost, Hypertension, = Nephrotoxicity=20 precludes its use for oral LP.

TACROLIMUS=20 :

=B7 =20 It is a = macrolide=20 antibiotic extracted from Streptomyces tsukubaensis

=B7 =20 A potent = immunosuppressive=20 agent, inhibiting T =96 cell activation at 10 =96 100 times lower = concentration than=20 cyclosporine. It inhibits calcineurin dependent activation of lymphokine = expression, apoptosis and degranulation

=B7 =20 Adult dose =96 = 150 =96 200=20 mg / kg / day

=B7 =20 Used topically, = it can=20 control symptoms and significantly improve refractory erosive OLP. Local = irritation is the most common side effect

=B7 =20 Tacrolimus = ointment 0.1%=20 is well tolerated and appeared to be effective in OLP that did not = respond to=20 topical steroids.

=B7 =20 However = discontinuation of=20 drug results in relapse.

3.=20 ANTIFUNGALS :

=20 Symptoms of oral LP may be exacerbated by candidal overgrowth or=20 infection, while antifungal treatment of erosive lesion with candida can = change=20 the lesions to the reticular form. Antifungal treatment in some cases of = oral LP=20 could reduce the potential of C. albicans to produce carcinogenic N =96=20 nitrosobenzyl methylamine.

=20 Symptomatic relief has been reported following use of = Amphotericin B,=20 Nystatin and Azole antifungals. Miconazole gel is found to be effective = during=20 topical steroid therapy in every case of oral lichen planus and is = useful as an=20 adjunctive therapy with topical steroids. Use of an antibacterial rinse = such as=20 chlorhexidine before steroid application helps prevent fungal = overgrowth.

4. RETINOIDS=20 : The retinoids have anti =96 = inflammatory properties, through their interactions with the arachidonic = acid=20 cascade. They stimulate macrophage activation and antibody dependent = cell=20 mediated immunity. May also reduce the CD₄ lymphocyte = infiltrate and=20 increase the macrophages in OLP lesion =96 thus accelerates=20 healing.

SYSTEMIC=20 RETINOIDS :

=B7 =20 System = isotretinoin has=20 been used successfully in severe erosive oral LP refractory to = conventional=20 therapies but relapses occurred within 2 months after the drug was = stopped.

=B7 =20 Fergusan et al = (1984)=20 concluded that etretinate in doses of 25 to 75mg d^-1for 2 = months was=20 of minimal value in the management of erosive LP. Common side effects = include=20 cheilitis, dryness of mucosa and increased transaminase level.

=B7 =20 Temarotene is a = retinoid=20 analogue with few adverse effects and has shown to be effective.

=B7 =20 An oral low dose = of=20 retinoid (all =96 trans =96 retinoic acid) has been used in recalcitrant = oral LP=20 with complete and partial remissions and without marked side effects.

TOPICAL=20 RETINOIDS :

=B7 =20 Topical = tretinoin 0.1% in=20 an adhesive gel (4 times a day for 2 months) and Topical isotretnoin = 0.1% (2=20 times per day for 2 months) can produce significant improvement in = patients with=20 oral LP. Only transient burning sensations or irritation on initial = application=20 have been reported and was controlled by reducing the number of = applications.=20 Moreover following treatment with topical tretinoin, histologic = examination=20 demonstrated that keratinization may decrease significantly or even=20 disappear.

=B7 =20 Topical 0.1% = Vit. A=20 rapidly eliminated white lesions of oral LP but all cases relapsed 2 =96 = 5 weeks=20 after discontinuation.

=B7 =20 Topical = fenretinide (200mg=20 d^-1 for 1 month) has proved to be beneficial in the treatment = of OLP=20 with minimal side effects, but not readily available. =

=B7 =20 A new topical = retinoid,=20 Tazarotene has been demonstrated to be useful in hyperkeratotic=20 OLP.

Possible side effects of systemic retinoid and = low=20 remission rates, dissuade the primary use of retinoids. Both systemic = and=20 topical retinoids should be used as adjuvant therapy = only.

5.=20 IMMUNOMODULATORS=20 :

Dapsone :=20 Dapsone should be considered = in=20 resistant cases of erosive OLP. Significant adverse effects such as = hemolysis=20 and headache precludes its use.

Interferon:=20 Topically applied gel = preparation=20 containing Human Fibroblast Interferon and Interferon =96 alpha have = suggested to=20 improve erosive oral LP. Development and exacerbation of oral LP during = and=20 after IFN =96 alpha therapy for HCV infection have been reported, = although=20 systemic IFN =96 alpha (3 =96 10 million IU thrice weekly) was = successfully used to=20 treat OLP in patients with and without HCV = infection.

Levamisole :=20 It has been used as an = immunomodulator=20 in OLP. Levamisole (150 mg d^-1 for 6 weeks) may be used as an = adjuvant medication during systemic steroid = treatment.

=20 The combination of levamisole and Chinese medicinal herbs can = achieve=20 complete remission more than either therapy given alone. However, = levamisole may=20 occasionally itself induce lichenoid lesions.

6. PSORALEN=20 AND ULTRAVIOLET A (PUVA) :

Ultraviolet irradiation, mainly in combination = with=20 psoralens, may suppress the cell mediated immunoreactivity in humans. = PUVA with=20 8 methoxypsoralen (0.6 mg Kg^-1) has many side effects such as = nausea,=20 dizziness, eye symptoms, paraesthesia and = headache.

=20 To avoid PUVA side effects, photosensitization with topical 0.01% = trioxsallen can be used for the treatment. An apparatus for light =96 = cured dental=20 fillings can be used as an irradiation source to deliver a beginning = dose of=20 0.75 Jcm^{- 2}and a total dosage ranging from 11.6 to 16.5 J=20 cm^-2. Photo = chemotherapy=20 may be useful for serve forms of erosive oral LP that do not respond to=20 conventional treatment.

=20 One matter of concern is that PUVA therapy has been shown to have = oncogenic potential; its use in the treatment of a pre =96 malignant = condition=20 like OLP could theoretically increase the risk of oral cancer. Further = study of=20 PUVA therapy for oral LP is needed.

7.=20 PHOTODYNAMIC THERAPY:

=20 Photodynamic therapy = is a=20 technique that uses a photosensitizing compound activated at a specific = wave=20 length of laser light to destroy the targeted cell via strong oxidizers, = which=20 cause cellular damage, membrane lysis and protein inactivation. The = exact=20 mechanism of action of PDT is unclear. It would appear to act on=20 hyperproliferating cells with selective uptake of photosensitizers into = these=20 cells it has been suggested that PDT may have immunomodulatory effects = and may=20 induce apoptosis. In the hyper proliferating inflammatory cells present = in=20 lichen planus this may reverse the hyperproliferation and inflammation = of lichen=20 planus.

=20 A phenothiazine dye methylene blue was described and attributed = to its=20 photodynamic properties. = Methylene=20 blue can be administered topically and orally and it may be a preferred = choice=20 for superficial lesions in skin and oral cavity. The fact that methylene = blue=20 has a strong absorption at wave length longer than 620 nm, where light=20 penetration into tissue is optimal, has led to the using of methylene = blue as a=20 promising candidate for PDT.

=20 5 =96 aminolaevulinic acid is also used as a photosensitizer = applied as a=20 thin layer of an oil in water emulsion. It remains localized to mucosal = layers=20 but it is a somewhat painful therapy. Further studies are need to = confirm the=20 efficacy of PDT in the treatment of oral lichen = planus.

Clinical=20 management of Oral Lichen Planus

FOLLOW =96=20 UP:

=B7 =20 Re examine every = month=20 during active treatment and monitor lesions for decrease in mucosal = erythema and=20 ulceration and alleviation of symptoms.

=B7 =20 Continue active = treatment=20 and try alternate therapies until erythema, ulceration and symptoms are=20 controlled.

=B7 =20 Follow up = alteast every 6=20 months

=B7 =20 Advice patients = to=20 regularly examine their mouth and seek the help of specialist if = symptoms are=20 increased or when lesions change.

PROGNOSIS:

=20 Symptomatic OLP characteristically waxes and wanes, although the=20 associated white patches do not resolve.

=20 In the context of appropriate medical care prognosis for most = oral LP is=20 excellent. Therefore continued surveillance, repeated biopsy, and (where = possible) eradication of erosive lesions and those lesions demonstrating = dysplastic changes remain the safest course. =20