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ORAL LICHEN PLANUS ORAL LICHEN PLANUS

ORAL LICHEN PLANUS - PowerPoint Presentation

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ORAL LICHEN PLANUS - PPT Presentation

Dr SAnandan Dean amp Professor of Dermatology SRMC amp RI Porur Chennai 600 116 OBJECTIVES Introduction Pathogenesis Heat shock protein in OLP Types of OLP Treatment modalities ID: 578788

olp oral erosive topical oral olp topical erosive treatment shock heat lichen effective protein side cell lesions systemic therapy

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Slide1

ORAL LICHEN PLANUS

Dr.

S.Anandan

,

Dean & Professor of Dermatology

SRMC & RI,

Porur

, Chennai – 600 116Slide2

OBJECTIVES

Introduction PathogenesisHeat shock protein in OLP.Types of OLP

Treatment modalities

Algorithmic approach Slide3

OLP

Chronic inflammatory disease of the oral mucosa 1-2% of the population is affected

50%

of patients with LP have oral lesions

Isolated oral LP seen in

15-35%

of casesSlide4

PATHOGENESIS

Expression of keratinocyte

self-antigen

Migration of CD8 lymphocytes into the epidermis

Activation of CD 8 cells through MHC 1 or CD4 cells by IL

2,12

IFN

γ

Apoptosis of basal keratinocte by TNFα, Fas-FasL, Granzyme B.Slide5

PATHOGENESIS

Upregulation of vascular adhesion molecule (lymphocyte homing)Matrix

metalloproteinases

(increase BM disruption)

RANTES(Regulated on Activation, Normal T cell Expressed and Secreted)

Mast cell

degranulation

– TNF-

α, chymase, tryptaseSlide6

6Slide7

OLP

Associated factorsInfections (eg.HCV)Drugs (NSAIDS,

sulfonylureas

, beta blockers, ACE inhibitors, etc.)

Contact allergens (dental amalgams)

Mechanical trauma Slide8

Role of HSP 90 in the pathogenesis and treatment of OLP

: A Molecular Research Work

8Slide9

CLINICAL SIGNIFICANCE

9Slide10

HEAT SHOCK PROTEINS

10

David Whitley, Heat Shock Proteins: A Review Of The Molecular Chaperones, Journal Of Vascular Surgery Volume 29, Number 4

http://www.britannica.comSlide11

HEAT SHOCK PROTEIN 90

11

David Whitley, Heat Shock Proteins: A Review Of The Molecular Chaperones, Journal Of Vascular Surgery Volume 29, Number 4Slide12

WHY THIS STUDY??

12Slide13

WHY HSP 90??

There has not been any studies done till date in India identifying the role of HSP 90 Oral Lichen planus

Based on the literature search, Identifying the Role of HSP 90 in Oral Lichen Planus shall help us in

providing us a prognostic tool as well pave way for further research in the field of targeted therapy.

13Slide14

METHODOLOGY

14Slide15

ROLE OF HSP

90 IN PATHOGENESIS OF OLP

1. Is

HSP

90

the gene causing keratinocyte autoantigenicity?

2. Over

Expression of the gene a role in carcinogenesis?15Slide16

RESULTS

Observations

Total

Mean

Variance

Standard deviation

P value

Group I (8)

7.0

0.8750

0.4107

0.6409

0.000

Group II (23)

43.00

1.86

0.2095

0.4577

16Slide17

NORMAL ORAL MUCOSA

Normal Tissue: (10x View: HE)

Score 1, Mild Intensity

(40x View: IHC)

ORAL LICHEN PLANUS

Section Showing Parakeratotic Epithelium With Basal Cell Degeneration With Intense Chronic Inflammatory Infiltrate (10x View:

H & E)

Section Shows

Score 2, Mild Intensity (10x View:

IHC

), (40x View: IHC)Slide18

18/23 cases(78.3%) had a score 2 and 19/23 cases (82.6%)with mild intensity.

Heat shock proteins expressed by oral keratinocytes may be auto antigenic in Oral lichen planus. Susceptibility to

Oral lichen planus may result from dysregulated heat shock protein gene expression

by stressed oral keratinocytes or from an inability to suppress an

immune response following self-Heat shock protein recognition.

Over expression of Heat shock protein

90

in Oral lichen Planus has been associated to the persistence or chronicity of the disease, or they could have simply reflected cellular injury.

The findings were substantiated with the study done by Bramanti T.E. et al (1995), Yin Cao Shen Li Jia et al (2006) and Ponlatham et al (2009), Yin Cao Shen Li Jia et al (2006) .

18Slide19

Positivity of staining was seen in the infiltrating lymphocytes in the lamina propria and few cells entering the epithelium due to basal cell degeneration

This finding is supported by the pathogenesis, cytotoxic CD8+ cells are responsible for the trigger mechanism. This finding also was concurrent with the results of the study done by

Ponlatham

et al

(2009),

Bramanti

T.E et al

(1995)

19Slide20

CONCLUSION

The results of the study support the role of Heat shock protein

90

in oral tumorigenesis and malignant

transformation.

Indeed

these finding pave the way for using

Heat

shock protein 90 as a marker protein for risk assessment in malignant transformation of oral lichen planus20Slide21

Types of oral LP

Reticular Erosive Atrophic

Plaque

BullousSlide22

Point of Interest

Skin Lichen Planus

Oral Lichen Planus

Clinical Aspects

Shiny,

Violaceous

Flat-topped polygonal papules

1. Bilateral white

lesion forming a lacework Beginning of the lesion

50%- Skin lesions without OLP

40%

- OLP followed by Skin lesions

25%

- Only OLP

Wickham’s strie

Positive

Positive

Main Symptoms

Itching

Burning

sensation and pain

22

Tony Burns, Steephen Breathnach, Rook’s Textbook of dermatology, 8

th

edition, Volume 2, Wiley-Blackwell, Chapter 41, Page 41.1-41.15Slide23
Slide24

OLPSlide25

OBJECTIVES OF TREATMENT

Identify interventions to treat OLPTo identify appropriate medications for management of different types of OLPSupport treatment measures with limited evidence.Slide26

Treatment options

CorticosteroidsRetinoids

Calcineurin

inhibitors

Immunosuppresive

agents

Immunomodulators

Antibiotics

PhototherapySurgerySlide27

Pharmacotherapy of OLP

Cochrane database systematic review – 2012RCT’s minimalHeterogenecity in trials

Design methods inappropriate

Different outcome variablesSlide28

Corticosteroids

TCS - First line therapy of OLPModulate inflammation and immune responseStabilizes the

lysosomes

Reduces lymphocyte activity Slide29

Corticosteroids

Midpotency

– Triamcinolone acetonide

0.1%

High potent –

Fluocinonide

acetonide

0.1%,

disodium

betamethasone phosphate

Superpotent – Clobetasol

propionate

In orabase- contains pectin, gelatin and

carboxymethyl

cellulose

Orabase substituted with adhesive paste used for dentures

Steroid mouth washes,

betamethasone

/

dexamethasoneSlide30

Systemic

Most useful in acute erosive oral LP or multisite disease

Pts unresponsive to

topicals

Upto

2

mg/kg/day of

prednisolone

can be given as a short courseMonitor for adverse effects

But studies show topical corticosteroids to be equally or more effective than systemic corticosteroids or the combination of the two.Slide31

Intralesional CTS

Used for localized resistant plaqueHydrocortisone, triamcinolone

acetonide

and

methylprednisolone

have been tried in various studies

Localized side effects like pain and mucosal atrophy. Slide32

Complications of TCS

Secondary

candidiasis

– Rx with topical

antifungals

(azoles)

Adrenal insufficiency (super potent)

Potential

tachyphylaxsisSlide33

Antifungals

Candida albicans in

37%

of oral LP lesions

Exacerbates the symptoms

Candida produce a carcinogen N-

nitrosobenzylmethylamine

Antifungal therapy can change erosive form to reticular form

Topical azoles can be used

Oral antifungals can be usedSlide34

Calcineurin inhibitors

Calcineurin inhibitorsCyclosporine

Tacrolimus

Pimecrolimus

Slide35

Tacrolimus

Inhibits T-cell activation at 10-100 times lower conc. than

CsA

Penetrates skin better than topical

cyclosporin

Tacrolimus 0.1% ointment +

ora

base

Significant improvement in refractory steroid unresponsive erosive oral LP

Side effect- local irritation Flare up after stopping therapy

Oral gel formulation available in IndiaSlide36

TIMS

1% Pimecrolimus

is also effective with low systemic side effects Slide37

Cyclosporin MOA

Inhibits the production of NFAT 1 transcription factor by calcineurin

Suppresses the cytokine production

It was found to be effective, applied as topical or mouth rinse in many studies but not all

Disadvantages – bad taste, transient burning sensation and high cost.

Swish and spit/swallow Slide38

Cyclosporin

was found to be as effective as triamcinolone acetonide in orabase

An alternative in the initial control of oral LP

Not a first line drug due to

high cost

serious side effects (hypertension,

nephrotoxicity

, etc.) availability of alternativesSlide39

Oral Cyclosporin

2.5 mg/kg body weight for 6 to 8 weeks (Acute erosive mucosal LP)Crisis buster

Watch for side effectsSlide40

Retinoids

Topical and systemic drugs usedTopicalIsotretinoin gel

0.1%

and

Tretinoin

oint

Produce significant improvement

Histological, decreased keratinizationTransient burning/irritation Slide41

Treatment of OLP

Topical fenretinideEffective with minimal side effects

Not readily available

Topical

tazarotene

Hyperkeratotic

oral LPSlide42

Systemic retinoids

IsotretinoinAcitretin

Due to side effect profile and low remission rates, used only as adjuvant therapy. Slide43

Steroid sparing agents

AzathioprineReported , effective in erosive and generalized oral LP

Used in severe recalcitrant disease, as steroid sparing agent

As effective as systemic steroids

Need to monitor for bone marrow suppression

Mycophenolatemofetil

-

1 to 1.5

gms per daySlide44

Treatment of OLP

AntimalarialsHydroychloroquine sulfate and

chloroquine

phosphate effective

But implicated in

lichenoid

reaction

Mesalazine

(5-aminosalicylic acid)Used in the Rx of IBDTopical mesalazine used as an adjuvantSlide45

Treatment of OLP

DapsoneIn erosive or bullous

LP, in resistant cases

Levamisole

Used as an

immunomodulator

Combined with low dose oral steroids in severe erosive LP

Can occasionally induce

lichenoid lesionsSlide46

Treatment of OLP

Low molecular weight heparinLow doses inhibits T lymphocyte heparinase

activity needed for T cell migration

suggested that the

immunomodulatory

molecules in heparin are probably sulfated disaccharides that act by inhibiting the production of the key

proinflammatory

cytokine

TNFαSlide47

Treatment of OLP

Interferon Topical human fibroblast interferon (Hu

IFN β) and interferon α

Effective in the erosive forms

Systemic IFN α

(3-10

million U thrice weekly)

In treatment of oral LP, esp. in HCV infected patientsSlide48

Biologicals

Efalizumab

Recombinant humanized monoclonal antibody

Monoclonal

Ab

to CD11a

inhibits T cell activation & trafficking in the skin Slide49

NON-PHARMCOTHERAPY

P-UVAEarlier oral 8-MOP was used as the photosensitizer

Now, topical

0.01%

trioxsalen

can be used to reduce the side effects

Useful for severe form of erosive oral LP resistant to conventional therapy

Carcinogenic potential of PUVA needs further study

Narrow band UVB studied in a few casesSlide50

LASER &PDT

CO2 laser

Multicentric

lesion and difficult areas of

oralLP

Recurrences have been reported

Excimer

308

nm laserEffective in the erosive OLP

Even in difficult to control lesions

Photodynamic therapy

With

methylene

blue

Case reports show

50%

improvement in lesionsSlide51

Oral LP and SCC

Incidence of

squamous

cell carcinoma in oral LP lesion ranges from

0.4% to 2%

Highest rates seen with

erythematous

and erosive lesions

Pathogenesis

Pro inflammatory cytokine rich environment

N-nitrosobenzylmethylamine carcinogen from Candida albicans

HCVSlide52

Surgery

Surgical excision Isolated non healing plaques and erosive lesionsSuspected malignant transformation

Free soft tissue graftsSlide53

Lifestyle modifications

Avoid smoking alcoholAvoid acidic/spicy food substances

To maintain good oral hygieneSlide54

Oral LP

Improve/control oral hygiene. Avoid precipitating factors, drugs, food chemicals, etc.

Erosive or symptomatic

Asymptomatic

Follow up every 6 months

No treatment

Smear for candida

Positive for Candida

Negative for Candida

Topical steroids

Topical steroids +

antifungals

Unsatisfactory response

Satisfactory response

Systemic steroid

Alternatives-

tacrolimus

,

retinoids

, PUVA,

ILS, steroid sparing drugs, DAPSONE, Non-pharmacotherapy

Maintenance with topical steroids

Unsatisfactory response Slide55

MY SUGGESTION

Algorithmic approach

Step 1: TCS/

Tacrolimus

in

orabase

Step 2: Continue Step 1 + Burst of Oral Corticosteroids

Step 3: Continue Step 1 + Cyclosporin

short course

Step 4: Continue Step 1 + MMF/Retinoids/Dapsone/ Non-PharmacotherapySlide56

THANK YOU