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Therapeutic Management of

Oral Lichen Planus: A Review for the Clinicians

Raghavendra Kini, DV Nagaratna, Ankit SahaJp journals, 2011, 2(3):

249- 253

Presented By Dr. Priyadershini A. Rangari

Introduction ORAL LICHEN PLANUS

Latin- Flat Algae Like

“leichen ruber“- described by Hebra.

"lichen planus“- Erasmus Wilson (1869)

Wickham noted the punctuations and striae . Age- 30-60 years Females> males. 0.5-2% of the population. It have premalignant potential and can progress to SCC(0.4%).

Resolves approximately in 1 year,

15% to 20% of cases follow a relapsing course

Kaz, R.W., Brahim, J, and Travis,W.D.oral squamous cell carcinoma arising in a patient with long-standing lichen planus. Oral Surg Oral Med Oral Pathol 70: 282-285, 1990.Sarah A. Gary G. Systemic Treatment of Cutaneous Lichen Planus: An Update, Cutis. 2011;87:129-134.

Etiology Cell-mediated immunologically induced degeneration of the

basal cell layer of the epithelium.

Immunologically induced lichenoid lesion is the common

denominator.

Stress, diabetes, hepatitis C, trauma, and hypersensitivity to

drugs and metals

In response to a variety of agents (eg, drugs, chemicals,

metals, and foods) “lichenoid” reactions to dental restorations,

Mouth rinses, antibiotics, gold injections for arthritis, and

immunocompromised status such as graft-versus-host disease.

Associated factors

BaganJ, et al. Topical therapies for oral lichen planus management and their efficacy: a narrative review. Current Pharmaceutical Design, 2012, 18, 5470-5480.

Clinical Features

Age- 5th decade F>M any oral mucosal site, mostly buccal mucosa. Pain or discomfort, which interferes with function and with

quality of life. The prevalence rate 0.1 and 2.2%. The frequency of malignant transformation ranges from

0.4% to 5.3% with the highest rate noted in erythematous and erosive lesions

Rajendran R. Oral lichen planus. J Oral Maxillofac Pathol 2005;9(1):3-5

Clinical Subtypes.

Reticular- lacelike keratotic mucosal configurations Atrophic - keratotic changes combined with mucosal

erythema Erosive - pseudomembrane- covered ulcerations combined

with keratosis and erythema Bullous – rare- vesiculobullous presentation combined with

reticular or erosive patterns

Reticular Plaquelike Erosive Papular Atrophic Bullous Papular form- Minute white papules which gradually

enlarge and coalesce to form either a reticular, annular, or plaque pattern.Parashar P. Oral Lichen Planus. OtolaryngolClin N Am. 44 (2011) 89-107

Burkit’s oral medicine 11th edi

Morphology Description

Reticular

Annular

(a) Slightly elevated fine whitish lines (Wickham’s striae) lacelike pattern or a pattern of fine radiating lines or (b) Annular lesions- 'Ring-shaped' lesions, develop gradually from single small pigmented spots into circular groups of papules with clear, unaffected skin in the center.10% cases.

Atrophic Inflamed areas of the oral mucosa covered by thinned red-appearing epithelium.

Bullous Rare and may sometimes resemble a form of linear IgA disease.

Ulcerative/ Erosive

Complication of the atrophic process after trauma or ulceration.Symptomatic- mild burning to severe pain. Central area of erosion with yellowish fibrinous exudate surrounded by erythema.

Burkit’s oral medicine 11th ediPaul C. Edward, oral lichen planus :clinical presentation and management,2002,68(8),494-99

Differential diagnosis

LeukoplakiaGraft vs host dsDiscoid lupus erythematosusChronic candidiasisMucous membrane pemphigoidChronic cheek bitingLichenoid reactionHypersensitivity mucositisWhite sponge nevus IgA reaction

Paul C. Edward, oral lichen planus :clinical presentation and management,2002,68(8),494-99

Treatment

Many patients with oral lichen planus may not have any

symptoms, in such cases there may be no need for active

treatment except for reassurance and periodic check-ups.

However, in many cases patients suffer from painful,

erythematous, erosive or bullous lesions which have a slight

predilection for transformation into oral squamous cell

carcinoma. Thus, the principal aim of treating OLP would be to

resolve the painful symptoms, the oral lesions and long-term

follow-up to counter the chances of transformation into

malignant lesions, especially for erosive and atrophic forms of

OLP, which are more prone for transformation.G. Lodi,Current controvercies in OLP: report of an international consensus meeting,

oral surg, oral path, oral med,2005;100:164-78

Corticosteroids The efficacy of corticosteroids for treatment of lichen planus is mainly

attributed to its anti-inflammatory and immuno-suppressive. These can

be used topically, intralesionally and systemically .

Topical corticosteroid therapy is usually the treatment of choice

initially, as it can be effectively delivered to the lesion surface with

minimal potential for systemic side effects.

flucocinonide,- 0.05%

clobetasol - 0.05% (Powercort cream, Clobenol cream),

Triamcinolone acetonide - 0.1% buccal paste form (Tess, Kenacort oral

paste, Cortrima cream),

These agents are either applied topically or rinsed (if in the form

of solution) 3-4 times/day after meal. Patients are advised not to

eat or drink for 30 minutes thereafter.

Dexamethosone and betamethasone valverate. 0.05% gel,

They are prescribed as gels, creams, ointment with orabase

(Kenalog in Orabase) or oral rinses.

Drugs which are available in orabase formulations are preferred

because of their tenacity on the oral mucosa leading to better

drug delivery.

Carhere M, Gass E, Carranza M, et al. Systemic and topical corticosteroids treatment of oral lichen planus. J Oral Pathol Med 2003;32(6):323-29.

Intralesional corticosteroids are reserved for cases

which do not respond to topical steroids.

10 to 20 mg of insoluble triamcinolone acetonide

(Avcort injection, Comcort injection) is diluted with 0.5

ml saline or lidocaine 2% then injected into the lesion,

which solubilize gradually and therefore have a

prolonged duration of action.

Silverman S Jr, Gorsky M, Lozda-Nur F. A prospective study of findings and management in 214 patients with oral lichen planus. Oral Surg Oral Med Oral Pathol 1991;72:665-70.

Systemic corticosteroids are indicated for short period when fail to

respond to topical steroids.

Prednisone (Wysolone) 40 to 80 mg daily for less than10 days without

tapering is advised

hydrocortisone 20 mg tab or triamcinolone 4 mg tab orally max 50

mg/day for five days.

If corticosteroids are used for prolonged therapy, they should not be

stopped abruptly. If done so, it can flare up the underlying disease for

which steroids were prescribed and cause acute adrenal insufficiency

because of HPA axis suppression.

Carhere M, Gass E, Carranza M, et al. Systemic and topical corticosteroids treatment of oral lichen planus. J Oral Pathol Med 2003;32(6):323-29.

combinations of more than one topical corticosteroid may be effectiveSystemic steroids and immunosuppressants prescribed for more severe cases would include:

Dexamethasone (Decadron) elixir 0.5 mg/5 ml Disp: 320 mlFor 3 days, rinse with 1 tablespoonful (15 ml) qid and swallow. For 3 days, rinse with teaspoonful (5 ml) qid and swallow. For 3 days, rinse with 1 teaspoonful (5 ml) qid and swallow every other time. Rinse with 1 teaspoonful (5 ml) qid and expectorate.Or

Prednisone tablets 10 mg Disp: 26 tabletsTake 4 tablets in the morning for 5 days, then decrease by 1 tablet on each successive day.

5days- 4 tab6th day 3 tab7th day 2tab8th day 1tabOr –Prednisone tablets 5 mg Disp: 40 tabletsTake 5 tablets in the morning for 5 days, then 5 tablets in the morning every other day until gone.

5 days 5 tab7th, 9th, 11th day….

Retinoids Systemic and topical retinoids have been employed to treat OLP.

Retinoids have antikeratinizing and immunomodulating effects.

Retinoids include the natural compounds and synthetic derivatives of retinol

that exhibit vitamin A activity.

Retinoids were synthesized by making minor structural changes.

First generation compounds include retinol, tretinoin and isotretinoin.

Second generation retinoids are synthetic analogs, which include etretinate

and acitretin.

Third generation retinoids include arotinoids, which currently are in

development.

As compared to systemic retinoids, topical retinoids are preferred and generally produce good Results.

Tretinoin is available in the form of 0.05% cream (Retino- A, Airol ). Isoretinoin is available as 0.05% gels (Sotret, Acno).

Buajeeb W, Kraivaphan P, Pobrurksa C. Efficacy of topical retinoic acid compared with topical flucinolone acetonide in the treatment of oral lichen planus. Oral Surg Oral Med Oral Pathol 1994;83:21-25.

Cyclosporin Cyclosporin is a very commonly used immunosuppressive drug

which belongs to a family of cyclicpolypeptides derived from the

fungus Tolypocladium inflatum.

It is basically used to prevent rejection in organ transplantation. It

inhibits chronic inflammatory reactions by inhibiting T-cell

activation and proliferation, also inhibits lymphokine production

and release of interleukin-2.

Topical ciclosporin can be used either in the form of mouthwashes or in

the form of adhesive base.

Patients are advised to swish and spit 5 ml of medication (l00 mg /ml)

three times daily for 8 weeks or 0.025% cyclosporin in an adhesive base

to apply four times daily, in some cases systemic cyclosporin has been

suggested.

orally-administered formulation, (Neoral), is available as a solution and

as soft gelatin capsules (10 mg, 25 mg, 50 mg and 100 mg).

(Immusol, Imusporin) 100 mg/ml oily solution (Katzung) and 100 mg/ml

oral rinse (Sandimmune)

Systemic- 8mg/kg/dayBuajeeb W, Kraivaphan P, Pobrurksa C. Efficacy of topical retinoic acid compared with topical flu. acetonide in the treatment of oral lichen planus. Oral Surg Oral Med Oral Pathol 1994;83:21-25.

Levamisole

Levamisole was developed in 1966 as an antihelmentic drug, but has

immunoregulating properties.

Mechanism of action of Levamisole has been found to Immunomodulate or

immunopotentiate T-cell mediated immunity.

Dose- Levamisole is administered at a dose of 50 mg three times/day for three

consecutive days per week for 4 to 6 weeks.

Levamisole (Ergamisol, Vermisol) is available as 50 mg,150 mg tab.

Lu Sy, Chen WJ, Eng HL. Dramatic response to levimisole and low dose prednisolone in 23 patients with oral lichen planus. Oral Surg Oral Med Oral Pathol 1995;80:705-09.

Azathioprine Azathioprine is a purine antimetabolite.

It has anti-inflammatory properties and decreases antibody production.

Azathioprine is reserved for patients who do not respond to other treatment

modalities. It can also be used in combination with corticosteroids and

cyclosporin.

When used in combination with corticosteroids, azathioprine can effectively

enhance corticosteroid immunosuppressive activity.

Thus, a lower dose of prednisone is required to achieve clinical efficacy and

thereby diminishing adverse effects of corticosteroids.

Azathioprine (Imuran, Azoprin)- 50 mg tab. started at 50 mg/day and can be

escalated up to 150 mg/day.

Tacrolimus Tacrolimus is a macrolide form of immunosuppressant derived from a type

of bacterium, Strepto. tsukubaensis. It inhibits the transcription of

interluekin-2 and transduction of signal to T-lymphocyte, and thus

effectively causing immuno-suppresion.

Its systemic use is comparable to corticosteroids but topical applications of

0.1% tacrolimus is proved to be far superior in treating of symptoms of oral

lichen planus than 0.05% clobetasol.

Recent studies by application of tacrolimus ointment 0.1% four times daily

for 4 to 8 weeks resulted in faster resolving of symptoms in oral lichen

planus as compared to topical corticosteroid application.

Topical- 0.1 to 0.3% (Tacroz Forte).Corrocher G, Di Lorenzo G, Martenelli N, et al. Comparative effect of tacrolimus 0.1% ointment and clobetasol 0.05% ointment in patients with oral lichen planus. J Clin Periodontol 2008;35:244-49.

Dapsone Dapsone should be considered in resistant cases of erosive OLP.

It has anti-inflammatory and immune-modulatory effects.

It is available as 5% gel (Acnesone)

25, 50 and 100 mg tab(Dapsone).

Dose - 100 mg orally in divided doses and may be increased at the rate

of 50 mg/day per week to a maximum of 300 mg/ day.

Giovanni Lodi, et al. Current controversies in oral lichen planus: Report of an international consensus meeting. (Part 2). Clinical management and malignant transformation. Oral Surg Oral MedOral Pathol Oral Radiol Endod 2005;100:164-78.

Interferon

Topically applied gel preparation containing human fibroblast

interferon and interferon-alpha have suggested to improve

erosive OLP. Development and exacerbation of OLP during and

after IFN-alpha therapy for HCV infection have been reported,

although systemic IFN-alpha (3-10 million IU thrice weekly) is

successfully used to treat OLP in patients with and without HCV

infection.

It is available as vials (Roferon-A) and syringes (Intafla-PF)

Mycophenolate Mofetil

It is an immunosuppressant used in treatment of patients with transplants.

It is available as 250 and 500 mg tablets (Baxmune) and 200 mg/ml

suspension (Cellcept).

Thalidomide It has been documented to have anti-inflammatory action in cases of auto-

immune disease Use of thalidomide as a regular line of treatment is not recommended,

unless all other treatment options have been exhausted. Its role in teratogenicity has to be remembered at all times.

Available as 100 mg capsules (Oncothal)

Dalmau J, Puig L, Roé E, Peramiquel L, Campos M, Alomar A. Successful treatment of oral erosive lichen planus with mycophenolate mofetil. J Eur Acad Dermatol Venereol 2007;21(2):259-60.Macario-Barrel A, Balguerie X, Joly P. Treatment of erosive oral lichen planus with thalidomide (French). Ann Dermatol Venereol 2003;130:1109-12.

PUVA Therapy Photosensitizing psoralen drug and UVA

radiation was introduced as a new therapy for oral mucosal lesions in

1987 by Jansen et al.

Psoralens belong to the furocoumarin class of compounds, which are

derived from fusion of a furan with a coumarin.

Four psoralens are used in PUVA therapy—psoralen, 5 methoxy psoralen

(Bergapten), 8-methoxypsoralen (Methoxsalen) and 4, 5, 8-trimethyl

psoralen (Trioxsalen). Ultraviolet irradiation in combination with

psoralens modulates the function of the cells of the immune system.

Psoralen(topical or systemic sensitizer)+ UVA(320-400nm) exposure

Nontherapeutic Options Photodynamic Therapy

Photodynamic therapy is a technique that uses a photosensitizing

compound activated at a specific wavelength of laser light to destroy the

targeted cell via strong oxidizers, which cause cellular damage, membrane

lysis and protein inactivation. It may have immunomodulatory effects and

may induce apoptosis.

Methylene blue can be administered topically and orally and it may be a

preferred choice for superficial lesions in skin and oral cavity. The fact that

methylene blue has a strong absorption at wavelength longer than 620 nm,

where light penetration into tissue is optimal, has led to the use of

methylene blue as a promising candidate for PDT.

Surgery and Lasers

Surgical excision, cryotherapy, CO2 laser and ND:YAG laser have all

been used in the treatment of OLP.

In general, surgery is reserved to remove high-risk dysplastic areas.

Excimer 308 nm laser is an effective choice for treatment of OLP

cases as it is well tolerated and painless when used.

Maintainance Avoidance of precipitating factors like spicy or acidic

foods, tissue trauma, and xerostomia- inducing

agents.

A "magic mouthwash" containing benadryl,

kaopectate (or carafate), and milk of magnesia as a

base to which nystatin and/or lidocaine may be added

for maintenance therapy.

When pt is not responding to corticosteroid and

triamcinolone CO2-LASER- lessens pain and burning

sensation, no recurrence upto 1 yr.

De magalhaes,, removal of OLP by CO2- LASER, Brazilian dent j.2011;22(6);522-6

HEPATITIS C VIRUS INFECTION AND ORAL LICHEN PLANUS

Hepatitis C Virus (HCV) may be an etiologic factor in OLP., The

characteristic band like lymphocytic infiltrate might thus be

directed toward HCV infected cells. Whether HCV infected patients

have increased risk of developing OLP or patients with OLP have

enhanced risk of developing HCV infection is yet to be answered.

The putative pathogenetic link between OLP and HCV still remains

controversial and needs a lot of prospective and interventional

studies for a better understanding

Sharma et al. Erosive Oral Lichen Planus and its Management: A Case Series, J Nepal Med Assoc 2008;47(170):86-90

Topical corticosteroids are the mainstay in treating mild to moderately

symptomatic lesions, include 0.05% betamethasone valerate gel,

0.05% fluocinonide gel, and 0.1% triamcinolone acetonide ointment.

The prophylactic use of a 0.2% Chlorhexidine gluconate rinse may help

reduce the incidence of fungal infection during corticosteroid therapy.

The depth of thermal damage for the CO2 laser extends from 50 to

100μm compared to 200 μm for Argon and 600 μm for the Nd: YAG

laser.19 Therefore, one can expect a lower risk with CO2 laser to the

periosteum and the underlying bone.

A double blind study of 28 pt with severe oral lichen plnus treated

with etretinate(75 mg daily) or a placebo for 2 mths, showed that

the retinoid had a marked beneficial effect.

Kjell H. Hakan M. Severe oral lichen planus: treatment with an aromatic retinoid, BJD, 2006, 23(5), 121-26

López J, Roselló Llabrés X, Cyclosporine A, an alternative to the oral lichen planus erosive treatment. Bull Group Int Rech Sci Stomatol Odontol.1995;38(1-2):33-8.

Presented a double-blind study in two groups afflicted with erosive oral

lichen planus of long evolution and resistant to other treatments.

In the group A he used mouthwashes with a 5 ml Cyclosporine A solution

to a 10% in olive oil of 0.4 degrees of acidity for 5 minutes, tds for 8

weeks.

In the control group he used acetonide of triamcinolone 01% in aqueous

solution.

After 2 weeks, Patients in group A improved considerably in their

symptomatology in a 90% against a 60% in group B.

Neeta Misra, Efficacy of diode laser in the management of oral lichen planus, BMJ Case Reports 2013; doi:10.1136/bcr-2012-007609

The patient with OLP lesions was treated using diode laser (940 nm) for

the symptomatic relief of pain and burning sensation.

The patient was assessed before, during and after the completion of the

treatment weekly. The treatment was performed for 2 months and the

patient showed complete remission of burning sensation and pain.

The follow-up was performed for 7 months and no recurrence of

burning sensation was found.

According to naturalnews.com

Aloe vera

A controlled trial published in the British Journal of Dermatology

confirmed empirical findings that aloe vera can effectively treat mouth

ulcers associated with oral lichen planus.

Patients who were given aloe vera topical applications reported 50%

improvement in symptoms and 33% of them reported that burning pain

in the mouth disappeared. Sciencedaily.com also supports the use of

aloe vera to alleviate the discomfort associated with oral lichen planus.

Aloe vera contains anthraquinones, chemical compounds that promote

healing and arrest pain because of their anti-inflammatory nature.

Bee Propolis

Bees use propolis, a natural resin found in young tree buds;

remetabolize it with their own nectar secretions to make a sealant to

build their hives. Bee propolis contains antimicrobial properties that are

effective in killing bacteria. Extracts of propolis can inhibit the growth of

bacteria, including Staphylococcus aureus, the cause of deadly

infections in hospital.

It is not only effective in fighting cavities, gingivitis, periodontal disease,

and reducing plaque buildup and bad breath, but it can also kill bacteria

and bring relief to oral lichen planus sufferers.

Petruzzi M, Lucchese A, Topical retinoids in oral lichen planus treatment: an overview. Dermatology. 2013;226(1):61-7.

Reviewed Sixteen studies (280 OLP patients topically treated with

different classes of retinoids) and concluded that topical

Isotretinoin was the most frequently employed retinoid in the

treatment of OLP. Particularly keratotic form better responds than

erosive form.

G. Lodi,Current controvercies in OLP: report of an international consensus meeting,oral surg, oral path, oral med,2005;100:164-78

€

Type Topical Systemic Surgical Maintainance

Reticular Usually self limited (8-12 months)

Lycopene

Atrophic Topical, flucocinonide,- 0.05% clobetasol - 0.05% (Powercort cream, Clobenol cream),Triamcinolone acetonide - 0.1% buccal paste form (Tess, Kenacort oral paste), 20-40mgIntralesional10 to 20 mg triamcinolone acetonide (Avcort inj) + 0.5 ml saline or lidocaine 2%

Asymptomatic-LycopeneretinoidsSymptomatic-steroidsOral prednisone (recurrence)Dapsone (50-150 mg daily)Resistant -ciclosporineAzathioprineLevamisoleTacrolimus Interferon

Not needed Avoidance of predisposing factors"magic mouthwash“ milk of magnesia + nystatin and/or lidocaine.

BullousErosive

Same as above Same as above PUVAPsycho-therapySurgery, cryotherapy, LASER

Same as above

Antioxidents & follow up

Symptomatic-Topical, flucocinonide,- 0.05% clobetasol - 0.05% (Powercort cream)Triamcinolone acetonide - 0.1% paste form (Tess, Kenacort oral paste), 20-40mg steroidsOral prednisone (recurrence)Dapsone (50-150 mg daily)

without symptoms Management of OLP

Intralesional10 to 20 mg triamcinolone acetonide (Avcort inj) + 0.5 ml saline or lidocaine 2%Systemic-

Steroidsprednisone (recurrence)Dapsone (50-150 mg daily

Resistant –ciclosporineAzathioprineLevamisoleTacrolimus Interferon

PUVAPsychotherapySurgery, cryotherapy, LASER

Avoidance of predisposing factors"magic mouthwash“ milk of magnesia + nystatin and/or lidocaineAntioxidents & follow up

With symptoms

Thank you