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Oral Submucous Fibrosis Dr Sanjana Ravindra Post Graduate RajaRajeswari dental College, Bangalore.

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Oral Submucous

FibrosisDr Sanjana Ravindra

Post Graduate

RajaRajeswari dental College,

Bangalore.

CONTENTS

Introduction

History

Definition

Epidemiology

Nomenclature

Etiopathogenesis

Clinical features

Classification

Histopathology

Differential

diagnosis

Diagnostic Criteria

Investigations

Management

Malignant Potential

Prognosis

Conclusion

References

INTRODUCTION

The oral cavity is lined with an

uninterrupted mucosa which is

continuous with the skin near

vermillion border of the lips and with

the pharyngeal mucosa in the region

of soft palate

INTRODUCTION

Inderbir Singh.Textbook of Human Histology 5th edition Jaypee Brothers Medical Publishers;2009

//www.google.co.in/search?q=oral+mucous+membrane

OMM- Unique area of the body, which is

continuously exposed to various kinds of stresses

such as heat, cold, microorganisms, chemicals and

mechanical irritations.

In response to these stresses, both epithelium and connective tissue layers of the oral mucosa exhibit acute and chronic reactive

changes

INTRODUCTION

POTENTIALLY MALIGNANT DISORDERS

INTRODUCTION

PRECANCEROUS LESION

A morphologically altered tissue in which

oral cancer is more likely to occur than in its

apparently normal counterpart

Leukoplakia

Erythroplakia

Mucosal changes associated with smoking

habits

Carcinoma in situ

Bowen’s disease

Actinic keratosis, cheilitis and elastosis

PRECANCEROUS CONDITION

A generalized state associated with a

significantly increased risk of cancer

Oral submucous fibrosis

Syphilis

Sideropenic dysplasia

Oral lichen planus

Dyskeratosis congenita

Lupus erythematosus

World Health Organization. Report of a meeting of investigators on the histological definition of precancerous lesions. Geneva: World Health Organization; 1973 Can 731.

ORAL POTENTIALLY MALIGNANT DISORDERS

INTRODUCTION

“It is a group of disorders of varying etiologies, usually tobacco;

characterized by mutagen associated, spontaneous or hereditary alterations

or mutations in the genetic material of oral epithelial cells with or without

clinical and histomorphological alterations that may lead to oral

squamous cell carcinoma transformation."

Sarode SC, Sarode GS, Tupkari JV. Oral potentially malignant disorders: Precising the definition. Oral Oncol 2012; 48: 759–760.

Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral

mucosa. J Oral Pathol Med 2007; 36: 575– 80.

1. HABIT RELATED

a. Tobacco associated lesions

b. Leukoplakia

c. Tobacco pouch keratosis

d. Stomatitis palatine nicotini

e. Betel nut associated

f. Oral submucous fibrosis

g. Sanguinaria-associated keratosis

2. NON-HABIT RELATED

a. Actinic cheilosis

b. Chronic candidiasis⁄

Group I: Morphologically altered tissue in which external factor is responsible for the etiology and malignant transformation.

Group II: Morphologically altered tissue in which chronici nflammation is responsible for malignanttransformation

IIA. CHRONIC INFLAMMATION CAUSED

BY INTERNAL DERANGEMENT.

1. Lichen planus

2. Discoid lupus erythematosus

IIB: CHRONIC INFLAMMATION CAUSED

BY EXTERNAL FACTORS.

1. Chronic mucosal trauma

2. Lichenoid reactions

3. Poor oral hygiene

4. Chronic infections

a. Chronic bacterial infections

b. Chronic viral infections

c. Chronic fungal infections

5. Other pathologies associated with prolonged

untreated chronic inflammation of the oral

cavity.

New classification of OPMD . Oral oncology head and neck 2011

INTRODUCTION

Group III: Inherited disorders that do notnecessarily alter the clinical appearance oflocal tissue but are associated with a greaterthan normal risk of PMD or malignanttransformation.

1. Inherited cancer syndromes

a. Xeroderma pigmentosum

b. Ataxia telangiectasia

c. Bloom syndrome

d. Fanconi’s anemia

e. Li Fraumeni syndrome

2. Dyskeratosis congenita

3. Epidermolysis bullosa

4. White sponge nevus

5. Darier’s disease

6. Hailey–Hailey disease

Group IV: No clinically evident lesion but oral cavity issusceptible to OSCC.

1. Immunosupression

a. AIDS

b. Immunosupression therapy (for malignancy or organ transplant)

2. Alcohol consumption and abuse

3. Nutritional deficiency

a. Sideropenic dysphagia

b. Deficiency of micronutrients

New classification of OPMD . Oral oncology head and neck 2011

INTRODUCTION

DEFINITION

DEFINITION

“Insidious chronic disease affecting any part of the oral cavity and

sometimes the pharynx. Although occasionally preceded by and /or

associated with vesicle formation, it is always associated with juxta-

epithelial inflammatory reaction followed by a fibro-elastic change of the

lamina propria with epithelial atrophy leading to stiffness of mucosa and

causing trismus and inability to eat”

-Pindborg JJ & Sirsat S.M (1966)

Pindborg JJ, Sirsat SM. Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol 1966; 22 (6):

764-779.

“Slowly progressive disease characterized by the fibrous

bands in the oral mucosa, ultimately leading to severe

restriction of mouth movement including the tongue.”

- World Health Organization (1978)

DEFINITION

World Health Organization Collaborating Centre for Oral Precancerous lesions. Definition of leukoplakia and related

lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978; 46: 518–39.

“ Slowly progressive chronic fibrotic disease of the oral cavity and

oropharynx, characterized by fibro elastic change and inflammation

of mucosa, leading to a progressive inability to open the mouth,

swallow or speak.”

( Burket's 10th edition )

DEFINITION

Bhattacharyya I. Red and White Lesions of the Oral Mucosa. Greenberg MS, Glick M eds. Burket's Oral Medicine. 10th ed. Spain: BC Decker Inc; 2003. 117-118.

HISTORY

HISTORY

Shushrutha, the greatest practitioner

of ancient medicine stated in his book

"Shushrutha Samhita' a condition

called 'Vidari' in his classification of

diseases of mouth and throat.

Ahuja SC and Ahuja U. Betel Leaf and Betel Nut in India: History and Uses. Asian Agri-History 2011;15(1):13–35.

First described among five East African women of Indian origin under the term Atrophia idiopathica(tropica) Mucosae Oris by Schwartz 1952

Joshi in 1952 is credited to be the first person who described it and gave the present term

“Oral sub-mucous fibrosis

In the year 1954, Su. 1. P. from Taiwan described similar condition, which he called "Idiopathic Scleroderma of mouth

HISTORY

SYNONYMS

SynonymsOral Submucous fibrosis of the palate and pillars (Joshi, 1952).

Atrophia idiopathica (trophica) mucosae oris. (Schwartz)

Diffuse oral submucous fibrosis (Lal 1953).

Idiopathic scleroderma of mouth (Su, 1954).

Submucous fibrosis of palate and cheek (Desa, 1957).

Idiopathic palatal fibrosis (Rao, 1962).

Submucous fibrosis of the palate (Sirsat and Khanolkar, 1962).

Juxta epithelial fibrosis (Pindborg J.J, Sirsat, 1964)

Oral submucous fibrosis (Pindborg and Sirsat, 1966).

Subepithelial fibrosis (Goleria, 1970).

Idiopathic oral fibrosis (Krishnamoorthy, 1970).

Asian Sideropenic Dysphagia (Ramanathan K, 1981)

Basoya S. Etiopathogenesis and management of oral submucousfibrosis. Quality in Primary Care

(2015) 23 (6): 327-332

EPIDEMIOLOGY

Epidemiology

Common in India, Indian subcontinents

Prevalence rate : India, Burma and South Africa : 0 to 1.2%

In India, overall incidence : 0.5%

High in southern parts of India, where the incidence of oral

cancer is also high

Africa Prevalence by gender

from 0.2-2.3% in males

and 1.2-4.57% in

females.

Age range : 20-45years

Malignant potential

rate: 7.6%

ETIOPATHOGENESIS

ETIOPATHOGENESIS

Local factors

Chilli

Arecanut

Misi

Systemic factors

Nutritional deficiency

Autoimmunity

Genetic susceptibility

Rajendran R.: Oral submucous fibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.

Etiopathogenesis

Capsicum annum & capsicum

frutescence

Active extract : Capsaicin

Vanillylamideof 8-methyl-6-

noneic acid

Active irritant

There are some ecological arguments against the

chilli hypothesis for example from Mexico or other

South American countries where chilli consumption

is widespread, there is no report of this condition.

The overall assessment is that there is no evidence

substantiating the etiologic role of chilli in OSMF

The suspicion that chilli is an etiological agent arose on the

basis of ecological observations and was strengthened by the

clinical and histological characteristics of this condition , i.e.

• Blood eosinophilia,

• Tissue eosinophils in the biopsy specimen

• Presence of sub epithelial vesicles

(suggested an allergic nature of this disease possibly due to

chilli intake.)

Chillies

It causes partial or complete degeneration of collagen into elastin like filaments- Sirsat

etal-1960

OSMF is the Asian version of siderophenicdysphagia where local irritant such as chillies

brings the changes-Ramanathan et al 1981

Rajendran R.: Oral submucous fibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.

Betel nut

Areca nut –unhusked

whole fruit of the areca nut

tree

Betel nut –inner karnel or seed which is obtained after removing husk

Common names:Betel nut or quid , Areca nut = EnglishThat Tha or Kun Ja = Myanmar (Burma)Supadi = NepaleseSupari = Hindi, BengaliAdike = KannadaMak or Mahk = ThaiPinlang, Pinang = China & Sarawak

India:o Paan , Paan-Gutkhao Paan masala (dry form, no tobacco)o Gutkhao Kwai (wet variety of betel-nut)

Etiopathogenesis

Botanical description:· Scientific name : Areca catechu Linnaeus· Family : Arecaceae (Palmae), palm family· Subfamily : Arecoideae

Lingappa A, Nappalli D, Sujatha GP, Shiva Prasad S. Areca nut: to chew or not to chew? e-Journal of Dentistry July - Sep 2011 Vol 1 Issue 3

The word ‘Areca’ isderived from the Malay word adakka (areca nut) or fromadakeya, the Indian equivalent

Arecanut

Alkaloids(0.2-0.7%) Flavanoids Others

Arecoline,

Arecaidine

Guvacine

Isoguvacine

Arecolidine

Guvacoline

Tannic acid,(14-

18%)

D. Catechol

Fats(3%)

Carbohydrates(47%

)

Proteins(5%)

Water (30%)

mineral matters

Stimulate cultured

fibroblasts to proliferate

and synthesize collagen.

Increase the stabilization of

collagen by enhancing the

cross linking of collagen

Composition of areca nut (Khanna JN, Andrade NN (1995)

lime

These cause local irritation and damage to the mucosa with vesicle

and ulceration on susceptible individual.

Lime in betel quid causes constant aberration of oral mucosa, allowing

direct access to the carcinogens

It is purified by soaking in lemon juice and then

prepared for use.

Lime is a calcium-containing inorganic material in which carbonates, oxides and hydroxides predominate (calcium oxide or calcium

hydroxide)Lime is obtained from lime stone

Aids in the digestion of food.Cures chronic diarrhea,

Etiopathogenesis

Tropical Pacific, Asia, and parts of east Africa.

Etiopathogenesis

The current production of arecanut in the world is about 0.613 million tonnes from an area of 0.476 million hectares.

India ranks first in both area (58%) and production (53%) of arecanut.

The current world productivity of arecanut is 1.287tonnes/ha.

China ranks first in arecanut productivity with 3.752 tonnes/ha.

India ranks fourth in terms of productivity (1.189 tonnes/ha).

Karnataka, Kerala, Assam and West Bengal are the important states growing arecanut.

Arecanut is mainly produced in Shimoga, South Kanara, North Kanara and Chickmagalore in Karnataka, Southern India

http://www.krishisewa.com/articles/production-technology/61-arecanut.html

WHY PEOPLE CHEW ??

Etiopathogenesis

Tobacco

Smoking form

Smokeless form

BidiChillumChuttaCigarette

DhumtiHookahHookli

KhainiManipuri TobaccoMishri/ MasheriPaanSnuffGudhakuZarda

Etiopathogenesis

Quid - A substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or

any manufactured or processed form’

N’-nitrosonornicotine is produced by bacterial and enzymatic nitrosation of nicotine and can be found by reaction of salivary nitrates with nornicotine

N’-nitrosonornicotine levels increased 44% when tobacco was mixed with saliva

N’-nitrosonornicotine extracted from chewing tobacco with saliva is approximately 1000 times that found in cigarette smoke

Etiopathogenesis

Smokeless tobacco KHAINI

Powdered sun-dried tobacco, slaked lime (CaOH2) paste mixture occasionally used with areca nut.

Placed in mouth/ chewed.

Commonly used - Maharashtra

MAINPURI TOBACCO

CONTAINS : tobacco, slaked lime, finely cut arecanut, camphor, cloves

Commonly used – Uttar Pradesh

Etiopathogenesis

PAAN

Refers to the betel leaf itself – quid

Quid contains : arecanut, lime, aniseed, cardamom, cinnamon, coconut, cloves, sugar, tobacco wrapped in betel leaf.

Etiopathogenesis

Etiopathogenesis

Misi is a black coloured powder containing various

chemical substances like washing soda, borax, powdered

alum, charcoal of myrobalan and fillers earth in varying

proportions which is used as cosmetic for the teeth and

gums.

Group of authors found 30 cases of OSMF in eastern

Uttar Pradesh, where villagers were constantly using

“Misi” as a cosmetic to keep their teeth clean and shiny.

In their study group

Misi

Ramachandran S, Annigeri RG, Sree Vijayabala G. Pathogenesis of Oral Submucous Fibrosis: The Past and Current Concepts. International Journal of Oral & Maxillofacial Pathology 2012;3(2):27-36.

Genetic

Predisposition

Collegen-related genes COL1A2, COL3A1,

COL6A1, COL6A3 and COL7A1 have been

identified as targets of transforming growth

factor-b (TGF- b) and induced fibroblasts at

an early stage of the disease

Basoya S. Etiopathogenesis and management of oral submucous fibrosis. Quality in Primary Care (2015) 23 (6): 327-332

Nutritional

deficiency

Repeated vesiculations and ulcerations

Vitamin B complex deficiency

Precipitated by the effect of defective nutrition due to impaired food intake in advanced cases

Impaired cellular utilization of iron explains the presence of hypochromic microcytic anemia.

Etiopathogenesis

Rajendran R.: Oral submucous fibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.

Due to resemblance to scleroderma

Female predominance

Age group

Presence of autoantibodies

Presence of circulatory immune complex (increased Ig complex)

Betal nut can act as heptans to produce antibodies to parietal cells

Autoimmunity

Rajendran R.: Oral submucous fibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.

PATHOGENESIS

Normal Oral MucosaIron and other nutritional

deficiencies

Tobacco, Lime and Betel nut

Genetic abnormalities

Autoimmunity

HSV/ HPV

Oral Submucous Fibrosis

Immune system changes

1) MULTIFACTORIAL - Pillai R Pathogenesis

Pillai R, Balaram P, Reddiar KS. Pathogenesis of OSMF. Relationship to risk factors associated with oral cancer. 2015; 69(8):2011-20.

A multifactorial model for the pathogenesis of OSF. Bold arrows show effects mediated by various factors through the immune system, whereas broken arrows show possible direct effects of the factors on oral mucosa.

2) Molecular Pathogenesis : Collagen Production Pathway (Rajalalitha S, Vali S. 2005)

Pathogenesis

Roberts AB, Flanders KC, Kondaiah P, Thompson NL, Van Obberghen- Schilling E, et al. Transforming growth factor

beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm

Res.1988; 44: 157-97.

Procollagenase

TGF-ß

Activation of PAI geneActivation of TIMP gene

PAI

Inhibits activated collagenases

TIMPs

Plasminogen Plasmin

Collagenase activity

Collagenase

Flavonoids in areca nut

Collagen Degradation

PAI- Inhibitor of Plasminogen Activator

Pathogenesis

Roberts AB, Flanders KC, Kondaiah P, Thompson NL, Van Obberghen- Schilling E, et al. Transforming growth factor

beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm

Res.1988; 44: 157-97.

TIMP -tissue inhibitor of matrix metalloproteinase

BMP- Bone Morphogenic ProteinPCP- Pro Collagen C ProteinaseLOX- Lysyl Oxidase

Pathogenesis

Roberts AB, Flanders KC, Kondaiah P, Thompson NL, Van Obberghen- Schilling E, et al. Transforming growth factor

beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm

Res.1988; 44: 157-97.

Overall effect of activated TGF –ß Pathway

Increase in collagen production

Decrease in collagen degradation

Increase in collagen (insoluble form)

Fibrosis

Oral Submucous Fibrosis

Pathogenesis

Roberts AB, Flanders KC, Kondaiah P, Thompson NL, Van Obberghen- Schilling E, et al. Transforming growth factor

beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm

Res.1988; 44: 157-97.

Increased collagen synthesis (by Arecaidine)

1. Fibroblast proliferation

2. Upregulated collagen genes

3. Upregulation of COX2

4. Increased profibrotic cytokines- TGF-β

5. Gene polymorphisms -TGF-β

Decreased collagen degradation

1. Resistant to degradation

2. Increased copper

3. Upregulation of Lysyl oxidase

4. Decreased obliteration (by Tannins)

5. Stabilization of collagen structure by Tannins

& Catachins

6. Stabilization of extracellular matrix

7. Inhibition of collagen phagocytosis

3) Angadi P et al. (2011)

Pathogenesis

Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.

Pathogenesis

Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.

Pathogenesis

Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.

Increase in collagen production

Decrease in collagen degradation

Increased collagen (insoluble cross-linking of insoluble form of collagen)

Fibrosis

Oral Submucous Fibrosis

Rajalalitha P, Vali S. Molecular pathogenesis of oral submucous fibrosis--a collagen metabolic disorder. J Oral Pathol Med. 2005 Jul; 34 (6): 321-8.

4) Muscle degeneration mechanism - Khanna JN, Andrade NN (1995)

Pathogenesis

Khanna JN, Andrade NN. Oral submucous fibrosis: a new concept in surgical management—report of 100 cases. Int J Oral Maxillofac Surg 1995;24(6):433-439

Kandasamy M, Anisa N, Rahman A, Rajan MA, Prakash A, Lal J. Etiopathogenesis of Oral Submucous Fibrosis - Review Of Literature. J Adv Med Dent Scie Res 2015;3(3):53-58.

5) Role Of Saliva – Salivary Coagulopathy- Chaturvedi VN et al (1991)

Normal mucosa

Slaked Lime Chronic Irritant

Chemical Burn

Microhaemorrhage

Laying down fibroblast

Coagulation

Salivary coagulation factor

Mechanical burn

Precipitate fibrosis

OSMF

Calcium

PlasmaFibrinogen

Altered immunity

Pathogenesis

Chaturvedi VN, Sharma AK, Chakrabarati S. Salivary coagulopathy and humoral response in oral submucous fibrosis. JIDA 1991;62:51- 9.

CLINICAL

FEATURES

Clinical features

Sex : both sexes.

Age : Majority of patients : 20-40 years

Sites: buccal mucosa, retromolar areas.

Soft palate, palatal fauces, uvula, tongue, labial mucosa.

Floor of mouth and gingiva

F>M• Shear et al 1967• Gupta et al 1978• Gupta et al 1980• Bailoor DN- 1993• Pindborg et al

1970

M>F• Wahi PN -1966• Pindborg et al

1967• Lai DR-1995

Sunken face appearance Trismus

Inability to blow Angular Cheilitis

Clinical features

BLANCHING Clinical features

Reticular blanching

Diffuse blanching

Localized blanching

Labial mucosa

Ventral surface Dorsal surface

Gingiva

Clinical features

Bud shaped uvula

Restricted tongue movement

Hockey stick appearance of uvula

Depapilated tongue Associated with premalignancy

MILD/ EARLY PHASE MODERATE PHASE LATE PHASE

Recurrent stomatitis and

vesiculation (palate)

Burning sensation to spicy

food

Mild blanching of oral

mucosa

No restriction of mouth

opening and tongue

movements, such as

protrusion

Burning sensation even

without stimuli

Blanching moderate to severe

Mouth opening and tongue

protrusion reduced by about

33%

Tongue is less flexible

Palpable bands present

Haematological examination:

mild anemia

Burning sensation continues

Severe blanching

Mouth opening and tongue

protrusion reduced by about

66%

Tongue may appear fixed and

cheek flexibility reduced

Thick palpable bands

Hematological examination:

iron deficiency anemia

Nutritional deficiency:

angular cheilitis

Mubeen. White lesions. In: Venkataraman BK. Diagnostic Oral Medicine.1st ed. Haryana: Wolters Kluwer Health; 2013. p. 91-99.

Clinical features

CLASSIFICATION /

GRADING/

STAGING

Classification / Grading/ Staging

More CB, Gupta S, Joshi J, Varma SN. Classification System for Oral Submucous Fibrosis. Journal of Indian Academy

of Oral Medicine and Radiology, January-March 2012;24(1):24-29

Classification / Grading/ Staging

Stage I: Stomatitis and vesiculation

Stage II: Fibrosis

Stage III: As its sequelae

Classification based on clinical features of OSMF

JV Desa (1957)

More CB, Gupta S, Joshi J, Varma SN. Classification System for Oral Submucous Fibrosis. Journal of Indian Academy

of Oral Medicine and Radiology, January-March 2012;24(1):24-29

Tupkari JV, Bhavthankar JD, Mandale MS. Oral submucous fibrosis (OSMF). A study of 101 cases. Journal of Indian Academy of Oral Medicine and Radiology 2007;19(2): 311-18.

Classification based on clinical features of OSMF

Pindborg JJ in 1989

•Stomatitis includes erythematous mucosa, vesicles, mucosal ulcers, melanotic mucosal pigmentation and mucosal petechiae.Stage I

•Fibrosis occurs in healing vesicles and ulcers, which is the hallmark of this stage.

•Early lesions show blanching of the oral mucosa.

•Older lesions include vertical and circular palpable fibrous bands in the buccal mucosa and around the mouth opening or lips.

•This results in a mottled marble like appearance of the mucosa because of the vertical thick, fibrous bands in association with a blanched mucosa.

•Reduction of mouth opening, stiff tongue, blanched and leathery floor of the mouth, fibrotic and depigmented gingiva, rubbery soft palate with decreased mobility, blanched and atrophic tonsils, shrunken bud like uvula and sunken cheeks, not commensurate with age or nutritional status.

Stage II

Classification / Grading/ Staging

Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58

Classification based on clinical features of OSMF

Pindborg JJ in 1989

• Sequelae of OSMF are as follows:

• Leukoplakia is found in more than 25% of individuals with OSMF.

• Speech and hearing deficit may occur because of involvement of tongue and the Eustachian tube.

Stage III

Classification / Grading/ Staging

Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58

Classification based on clinical features of OSMF

SK Katharia et al (1992)

SCORE MOUTH OPENING / INTERINCISAL DISTANCE IN mm

0 41 or more

1 37-40

2 33-36

3 29-32

4 25- 28

5 21-24

6 17-20

7 13-16

8 09-12

9 05-08

10 0-04

Classification / Grading/ Staging

Katharia SK, Singh SP, Kulshreshtha VK. The effects of placenta extract in management of oral submucous fibrosis. Indian Journal of Pharmacology 1992;24;181-83.

Classification based on clinical features of OSMF

Group A: >35 mm

Group B: Between 30 and 35 mm

Group C: Between 20 and 30 mm

Group D: <20 mm

Lai DR (1995)

Classification / Grading/ Staging

Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58.

Classification based on clinical features of OSMF

R Maher et al (1996)

Involvement of one-third or less of the oral cavity (if three or less of the

above sites are involved).

Involvement of one to two-thirds of the oral cavity (if four to six intraoral

sited are involved).

Involvement of more than two-thirds of the oral cavity (if more than six

intraoral sites are involved).

Classification / Grading/ Staging

More CB, Gupta S, Joshi J, Varma SN. Classification System for Oral Submucous Fibrosis. Journal of Indian Academy

of Oral Medicine and Radiology, January-March 2012;24(1):24-29

Classification based on clinical features of OSMF

Haider et al. (2000)Clinical staging:

- Stage 1: faucial bands only

- Stage 2: faucial & buccal bands

- Stage 3: faucial, buccal & labial bands

Functional staging:

- Stage 1: mouth opening >20 mm

- Stage 2: mouth opening 11-19 mm

- Stage 3: mouth opening <10 mm

Classification / Grading/ Staging

Haider SM, Merchant AT, Fikree FF, Rahbar MH. Clinical and functional staging of oral submucous

fibrosis. Br J Oral Maxillofac Surg. 2000 Feb;38(1):12-5.

Classification based on clinical features of OSMF

Group I: Only symptoms, with no

demonstrable restriction of mouth

opening.

Group II: Limited mouth opening 20

mm and above.

Group III: Mouth opening less than

20 mm.

Group IV: OSMF advanced with limited mouth

opening. Precancerous or

cancerous changes seen throughout the

mucosa.

Ranganathan K et al (2001)

Classification / Grading/ Staging

Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58.

Classification based on clinical features of OSMF

Rajendran R (2003)

EARLY OSF: Burning sensation in the mouth. Blisters especially on the palate, ulceration or recurrent generalized

inflammation of oral mucosa, excessive salivation, defective gustatory sensation and dryness of mouth.

ADVANCED OSF: Blanched and slightly opaque mucosa, fibrous bands in buccal mucosa running in vertical direction.

Palate and faucial pillars are the areas first involved. Gradual impairment of tongue movement and difficulty in mouth

opening.

Classification / Grading/ Staging

George Antony, Sreenivasan BS, S Sunil, et al. Potentially malignant disorders of oral cavity. Journal of Oral and Maxillofacial Pathology 2011;2(1):95-100.

Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58.

Classification based on clinical features of OSMF

Nagesh and Bailoor (1993)

Stage I early OSMF: Mild blanching, no restriction in mouth Burning sensation on taking spicy food or hot beverages.

Stage II moderate OSMF: Moderate to severe blanching, mouth opening reduced by 33%, cheek flexibility reduced, burning sensation also in absence of stimuli, palpable bands felt. Lymphadenopathy either unilateral or bilateral and demonstrable anemia on hematological examination.

Stage III severe OSMF: Burning sensation is very severe patient unable to do dayto- day work, more than 66% reduction in the mouth opening, cheek flexibility and tongue protrusion. Tongue may appear fixed. Ulcerative lesions may appear on the cheek, thick palpable bands and lymphadenopathy bilaterally evident.

Classification / Grading/ Staging

Bailoor D, Nagesh KS. Fundamentals of oral medicine and radiology (1st ed),2005.

Classification based on clinical features of OSMF

Group A—mild cases: Only occasional symptoms, pallor, vesicle formation, presence of one or two solitary palpable bands, loss of elasticity of mucosa, variable tongue involvement with protrusion beyond vermillion border. Mouth opening >3 cm.

Group B—moderate cases: Symptoms of soreness of mucosa or increased sensitivity to chilies, diffuse involvement of the mucosa, blanched appearance, buccal mucosa tough and inelastic fibrous bands palpable, considerable restriction of mouth opening (1.5 to 3 cm) and variable tongue movement.

Group C—severe cases: Symptoms more severe, broad fibrous bands palpable, blanched opaque mucosa, rigidity of mucosa, very little opening of mouth (less than 1.5 cm), depapillated tongue and protrusion of tongue very much restricted.

Tinky Bose and Anita Balan (2007)

Classification / Grading/ Staging

Bose Tinky, Balan Anita. Oral submucous fibrosis-A changing scenario. Journal of Indian Academy of Oral Medicine and Radiology 2007;19(2):334-40.

Classification based on clinical features of OSMF

Stage I: Mouth opening >45 mm

Stage II: Restricted mouth opening 20 to 44 mm

Stage III: Mouth opening <20 mm

Kiran Kumar et al (2007)

Classification / Grading/ Staging

Kumar Kiran, Saraswathi TR, Rangnathan K, Devi Uma M, Elizabeth Joshua. Oral submucous fibrosis: A clinicohistopathological study in Chennai. Indian Journal of Dental Research 2007;18(3):106-11.

Classification based on clinical features of OSMF

Chandramani More et al (2011)

Stage 1 (S1)

•Stomatitis and/or blanching of oral mucosa.

Stage 2 (S2)

•Presence of palpable fibrous bands in buccal mucosa and/or oropharynx, with /without stomatitis.

Stage 3 (S3)

•Presence of palpable fibrous bands in buccal mucosa and/or oropharynx, and in any other parts of oral cavity, with/ without stomatitis.

Stage 4 (S4)

•a. Any one of the above stage along with other potentially malignant disorders, e.g. oral leukoplakia, oral erythroplakia, etc.

•b. Any one of the above stage along with oral carcinoma.

Clinical staging

Classification / Grading/ Staging

Reddy V, Wanjari PV, Reddy N, Reddy P. Oral Submucous Fibrosis: Correlation of Clinical Grading to various habit

factors. International Journal Of Dental Clinics 2011:3(1): 21-24.

Classification based on clinical features of OSMF

Chandramani More et al (2011)

M1

• Interincisalmouth opening up to or greater than 35 mm.

M2

• Interincisalmouth opening between 25 and 35 mm

M3

• Interincisalmouth opening between 15 and 25 mm

M4

• Interincisalmouth opening less than 15 mm.

Functional staging

Classification / Grading/ Staging

Reddy V, Wanjari PV, Reddy N, Reddy P. Oral Submucous Fibrosis: Correlation of Clinical Grading to

various habit factors. International Journal Of Dental Clinics 2011:3(1): 21-24.

Prakash R. et al

Based on morphologic variants of soft palate

Type 1: Leaf shaped

Type 2: Rat tail shaped

Type 3: Butt shaped

Type 4: Straight line

Type 5: Deformed S

Type 6: Crook shaped

Classification / Grading/ Staging

Classification based on Histopathological features of OSMF

Pindborg JJ and Sirsat SM (1966)

VERY EARLY STAGE:

Finely fibrillar collagen dispersed with marked edema. Plump young fibroblast containing abundant cytoplasm.

Blood vessels are dilated and congested.

Inflammatory cells, mainly polymorphonuclearleukocytes with occasional eosinophils are found.

EARLY STAGE:Juxta-epithelial area shows early hyalinization. Collagen still in separate thick bundles.

Moderate number of plump young fibroblasts is present.

Dilated and congested blood vessels.

Inflammatory cells are primarily lymphocytes, eosinophils and occasional plasma cells.

MODERATELY ADVANCED STAGE:

Collagen is moderately hyalinized.

Thickened collagen bundles are separated by slight residual edema.

Fibroblastic response is less marked.

Blood vessels are either normal or compressed.

Inflammatory exudate consists of lymphocytes and plasma cells.

ADVANCED STAGE:

Collagen is completely hyalinized.

Smooth sheets with no separate bundles of collagen is seen.

Edema is absent.

Hyalinized area is devoid of fibroblasts.

Blood vessels are completely obliterated or narrowed.

Inflammatory cells are lymphocytes and plasma cells.

Classification / Grading/ Staging

Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58.

Classification based on Histopathological features of OSMF

Kiran Kumar et al (2007)

1. Grade I: Loose, thick and thin fibers

2. Grade II: Loose or thick fibers with partial

hyalinization

3. Grade III: Complete hyalinization

Classification / Grading/ Staging

Kumar Kiran, Saraswathi TR, Rangnathan K, Devi Uma M, Elizabeth Joshua. Oral submucous fibrosis: A clinicohistopathological study in Chennai. Indian Journal of Dental Research 2007;18(3):106-11.

HISTOPATHOLOGICAL

FEATURES

Histopathological features

Rooban T, Saraswathi TR, Al Zainab FH, Devi U, Eligabeth J, Ranganathan K. A light microscopic study of fibrosis involving muscle in oral submucous fibrosis. Indian J Dent Res 2005;16:131.

DIFFERENTIAL

DIAGNOSIS

ANEMIC STOMATITIS: because of presence of

Dysphagia concomitant with OSMF, patient will

have reduced diet and hence nutritional deficiency and finally resulting anemia

SCLERODERMA: a connective tissue disorder resulting in trismus and

stiffness of mucosa

RADIATION FIBROSIS: if the patient gives history of

radiation therapy

VERTICAL SCAR BAND: if patient gives history of minor or major surgical

procedures

Differential

Diagnosis

DIAGNOSIS

Diagnosis

HISTORY OF BETEL QUID CHEWING

INTERNATIONAL CONSENSUS

CRITERIA

LABORATORY INVESTIGATIONS

Palpable fibrous bandsMucosal texture feels

tough & leatheryBlanching of mucosa

together

Decreased Hb, iron, protein and vitamin B complex levels

Increased erythrocyte sedimentation rate

Assessment of tongue protrusion

Kumar SM, Shanmugam S. Ramalakshmi M, Jayashankar S. Various treatment modalities and visceral organ involvement (cardiac) in oral submucous fibrosis. A clinical study. JIAOMR 2011;23(3) 190-194

Diagnosis

Subject will be asked to protrude the tongue, as much as possible at maximal mouth

opening.

Distance between mesio-incisal angle of upper / lower left incisors and tip of tongue will

be measured.

If incisors are absent, crest of lower alveolar ridge will be taken as the point of reference.

Three measurements will be taken and the average value will be calculated and recorded.

Two points measured between at 1/3 rd the distance from the angle of mouth on a line joining the tragus of ear & angle of mouth

Subject is then asked to blow his cheek fully & the distance measured between the 2 points marked on the cheek

Males 1.3 cm

Females 1.08 cm

Assessment of cheek flexibility

Diagnosis

CF = V1 – V2

DiagnosisAssessment of mouth opening

MEAN INTERINCISAL

DISTANCE

Male: 51.3 mm (Range 39–65 mm)

Female: 44.3 mm (Range 36–56 mm)

{Indian males is 51.3±8.3 mm,

females is 44.3±6.7 mm}

Mezitis M, Rallis G, Zachariades N. The normal range of mouth opening. J Oral Maxillofac Surg.2015;47:1028.

INVESTIGATIONS

INVESTIGATIONS

Hematological & Biochemical

Serological

Cytogenetics

Histopathological

Immunohistochemical

Immunofluorescence

Tissue Culture

INVESTIGATIONS

VitaminB 12, folate and iron

Anaemia

Eosinophilia

serum iron

Decrease in Increase in total iron-binding capacity

blood sedimentation rate

Gammaglobulin

serum Mucoproteins, Mucopolysaccharides

Anti-streptolysin titre 0 (measured in Todd's units

LDL, VLDL

• Albumin• Lactate dehydrogenase

iso-enzyme ratio (LDH IV/LDH II)

• Serum copper and zinc ratio

• Lipid profile • HDL , total cholesterol

Hematological & Biochemical

2) Serological 1. ↑ High-affinity rosette forming cells (HARFC)

2. ↑ Serum levels of IgA, IgD and IgE (Rajendran R

et al- 1986)

3. HLA typing(A10, B7, DR3) (Caniff et al 1981)

4. ↑ β2 microglobulin (Anil S et al 1995)

3) Cytogenetics 1. Sister chromatid exchange (SCE)

2. AgNOR. Silver-binding nucleolar organizer

region proteins (AgNORs)

3. Transforming growth factor- β-1 ( infrequent but

exist in selected loci in OSMF)

INVESTIGATIONS

4) Immunohistochemistry 1. ↑ Cytokeratin (CK-2)-

2. ↓CK-17- lalii A et al

3. ↑ Cystatin C - Tsai CH et al -2007

4. ↑ Basic fibroblast growth factor- in early stages -Bishen KA et al

5. ↑ Heat shock protein 47 (by RT-PCR) - Yang SF et al – 2008

6. ↑ TIMP1, 2, PAI – 1 - Shung-FA et al

7. ↑ p53- Chiang CP

8. ↑ Retinoic acid receptor beta (RARbeta)- Kaur J et al -2004

5) Immnofluorescence 1. Hyalinized stroma can be distinguished from the

Amyloid infiltration of Amyloidosis

2. Using :

3. Congo red staining and

4. Thioflavin-T staining

INVESTIGATIONS

MANAGEMENT

MANAGEMENT

Preventive

measures

Medical treatment

Physical therapy

Surgical treatment

MANAGEMENT

Preventive measures

Medical treatment

Physical therapy

Surgical treatment

HABIT COUNSELING MANAGEMENT

they’re

patients

MANAGEMENT

Preventive measures

Medical treatment

Physical therapy

Surgical treatment

Antioxidants : b-carotene, vitamins A, C and E, zinc

Lycopene

Curcumins

Oxitared capsule

Nutrients, Micronutrients and Anti-

oxidants

Biogenic stimulation

Placental extract

Proteolytic enzymes

• Collagenase

• Hyaluronidase

IM

MU

NE

MO

DU

LA

TIO

NTopical

Betamethasone

Triamcinolone acetonide

Intralesional

Chymotrypsin

Interferon gamma (IFN-γ)

Hydrocortisone

Betamethasone

Methylprednisolone

Triamcinolone diacetate

Dexamethasone

Systemic

Levamisole

Immune milk

Colchine

1. Pentoxifylline

2. Nylidrin hydrochloride

Promotion of blood flow

b-carotene, vitamins A, C and E, zinc

Lycopene

Curcumins

Oxitared capsule

Nutrients, Micronutrients and Anti-oxidants

Antioxidants are protective agents that inactivate reactive oxygen species and therefore significantly delay or prevent oxidative damage

Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent.

Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions.

ANTIOXIDANTS

Antioxidants such as superoxide dismutase, catalase and glutathione peroxidase are naturally present within human cells

In addition, antioxidants such as vitamin E, vitamin C, polyphenols and carotenoids are available from food.

Rui L et al Lycopene: features and potential significance in the oral cancer and precancerous lesions J Oral Pathol Med 2011;40: 361–368

Kelkel M et al. Antioxidant & antiproliferative propertiesv of lycopene. Free radical research, 2011;45(8):925-940.

The antioxidant potential has been ranked as followslycopene > α-tocopherol > α-carotene > ß-cryptoxanthin > zeaxanthin= ß-carotene > lutein

ANTIOXIDANTS

Beta carotene

Hydrophobic molecules with little

or no solubility in water

Dark green, orange or yellowish vegetables,

such as spinach, carrots, sweet potato, mango, papaya, and

oranges

Vitamin A precursor

Antioxidizing action-ligation between

beta-carotene and oxygen, which is an

unstable reactive molecule, thus

diminishing the damaging effects of

free radicals

ANTIOXIDANTS

Maintains epithelial integrity

Plays an important role in induction and control of epithelial differentiation in mucous secretory and keratinization tissue,

Basal cells are stimulated to produce mucous secreting cells.

The progress of premalignant cells to malignancy is delayed or arrested.

It improves the mucosal colour, reduction of fibrous bands and improvement in mouth opening.

Vitamin A

Usage: Vitamin A 50,000 IU orally daily (12Weeks)

ANTIOXIDANTS

Zinc

Epithelializing agent

Dosage : Zinc sulphate 220mg TDS

Zinc alone /in combination with vitamin-A better in grade I & II

Zinc + cortisone effective in grade III

Increases the extent of relief and no relapse was observed upto a period

of 15 months

• Acts as antioxidant prevent formation of toxic substances and enhance the indigenous concentration of Vitamin A.

• Vitamin E by enhancing the concentration of Vitamin A helps in improvement of mucosal color, burning sensation ,and mouth opening.

Vitamin E

ANTIOXIDANTS

Vitamin B complex with iodine (injection

ranodine)

1. I.M -2ml daily

2. Contains

Methyl tri oxyethyl iodomine

Vitamin B1- 1mg

Vitamin B6-0.3 mg

Vitamin B2- 0.6mg

Nicotinamide- 15 mg

Calcium pantothenate- 1mg

Vitamin B-complex tablets

1. Orally in a dose of 200 mg twice a day

ANTIOXIDANTS

Beta carotene- 10mg

Zinc sulphate monohydrate-27.45mg

Monohydrated selenium dioxide- 70mcg

Manganese sulphate- 2mg

Copper sulphate- 1mg

ANTIOXIDANTS COMBINATIONS

Antoxid (Capsule)

ANTIOXIDANTS

Alpha - lipoic acid is a sulfur-containing substance that is readily converted to and from its reduced form, dihydrolipoic acid.

Alpha - lipoic acid acts as a coenzyme in reactions that occur in the Krebs cycle; specifically it is involved in the decarboxylation of pyruvate and some other alpha-keto acids.

It may well be the perfect antioxidant. Alpha - lipoic acid has researched for use in the treatment of HIV and diabetes

Because it dissolves in both water and fat, this so-called "universal antioxidant" is able to scavenge more wayward free-radical cells than most antioxidants, the majority of which tend to dissolve in either fat or water but not both.

α-Lipoic AcidANTIOXIDANTS

b-carotene, vitamins A, C and E, zinc

Lycopene

Curcumins

Oxitared capsule

Nutrients, Micronutrients and Anti-oxidants

Antioxidants

Lycopene ANTIOXIDANTS

Lycopene is a bright red carotenoid pigment.

Its name is derived from the tomato's species classification Solanum lycopersicum

Tomatoes, watermelons, guava,graves,

red chilli

Tomato & tomato-based food – 85%

Lycopene - carotenoid, acyclic isomer of β-carotene,highlyunsaturated hydrocarbon containing 11 conjugated and two unconjugated double bonds

induced by light, thermal energy, and chemical reactions, it can also form cis–trans isomers including 15-, 13-, 11-, 9-, 7-, 5-cis isomers .

The lycopene isomers found in human blood plasma, breast milk, and tissues are presented as isomeric mixture, with 50% as cis isomer type

Structure & properties of lycopene AO activity

Inhibition of cancer cell proliferation

Interference with growth factor stimulation

Regulation of transcription and

Restoration of gap junctions.

B

E

N

E

F

I

T

S

O

N

H

U

M

A

N

H

E

A

L

T

H

Rao A.V., Ray M.R, Rao L.G. Lycopene .Advances in food and nutrition research. 2006 3(51):100-164

Agarwal A,Roa A .Tomato lycopene and its role in human health & chronic diseases . CMAJ.2009;163(6)

Lycopene

Formulations

1. LYCOSTAR

2. LYCORED

3. LYNET

4. LYCORICH

5. LYCO-FIRST

6. LYCOAGE

7. LYCOBEL

8. LYCOBIG

9. LLYCOGOLD

10. LYCOLIFE

11. LYCOR

16 mg of lycopene daily in 2 equally divided doses

Kumar A et al, 2007

2000µg of lycopene twice daily for 3 month.

Gowda B et al 2011

DOSES

Selenium 75mcg

Lycopene 5000 mcg

Caratenoids10.33 mcg

Zinc 27.33mcg

Calcium ascorbate 50

mcg

Wheat germ oil 25mcg

Beta carotene:30mg

Selenium dioxide:200mcg

Zinc sulphate:27.5mg

Manganese:2mg

Copper:1mg

Alpha lipoic acid 50 MG

Beta-carotene 10 MG

Elemental copper 1 MG

Elemental selenium 75

MCGLycopene 5 MGVitamin E 10 IU

Zinc sulphate 27.45 MG

Lycopene 15 mg Zinc 5 mg

Vitamin C 40 mg Vitamin D

20 mcg

b-carotene, vitamins A, C and E, zinc, copper, manganese and selenium

Lycopene

Curcumins

Spirulina

Oxitared capsule

Nutrients, Micronutrients and Anti-oxidants

ANTIOXIDANTS

ANTIOXIDANTS

Das D, Balan A, Sreelatha KT. Comparative Study of the Efficacy of Curcumin and Turmeric Oil as Chemopreventive Agents in Oral Submucous Fibrosis: A Clinical and Histopathological Evaluation. Journal of Indian Academy of Oral Medicine and

Radiology, April-June 2012;22(2):88-92.

Curcumin is active ingrediant of turmeric.

Curcumin

ACTIONS

Anti-inflammatory

Antioxident

Fibrinolytic

Inhibition of lipid peroxidation

Checking cellular proliferation/

promotes apoptosis

Inhibition of collagen synthesis

DOSE

500mg

twice

daily

Das D et al-2011Significant improvement was observed in the clinical sign, symptoms and even

histopathologically.

Antioxidants (b-carotene, vitamins A, C and E, zinc, copper, manganese and selenium)

Lycopene

Curcumins

Oxitared capsule

Nutrients, Micronutrients and Anti-oxidants

Contents

Amra (Mangifera Indica)

Ashwagandha (Withania Somnifera)

Garjara (Daucus Carota)

Yashtimadhu (Glycyrrhiza Glabra)

Draksha (Vitis Vinifera)

Amalaki (Emblica officinalis)

Lavanga (Syzygium Aromaticum )

ANTIOXIDANTS

Oxitard

Doses2 capsules twice daily for

period of 3 month

Biogenic stimulation

Placental extract

Proteolytic enzymes

• Collagenase

• Hyaluronidase

Biogenic stimulation

PLACENTAL EXTRACT

Proteolytic enzymes

• Collagenase

• Hyaluronidase

Placental extract

Placentrex was first introduced By Flator(1933) and later developedin 1953. It owes its inception to corneal transplant.

ACTIONS OF PLACENTREX

• Accelerates cellular metabolism.

• Aids in absorption of exudates.

• Stimulates regenerative process.

• Increase physiological function of

organs.

• Produces significant

enhancement of wound healing.

• Has anti-inflammatory effect

FLATOR THEORY

“Animal and vegetable tissues whensevered from the parent body and exposedto a condition unfavorable, undergobiological re-adjustments leading to thedevelopment of substances in state oftheir survival to ensure their vitality asBIOGENIC STIMULATORs.Such tissues or their extracts whenimplanted or injected into the body afterresistance to pathogenic factorsstimulates metabolic or regenerativeprocess thereby favoring recovery.”

It is an aqueous extract of human placenta that contains nucleotides, enzymes, vitamins, aminoacids & steroids.

Thakur.G et al.Does Topical Application of Placental Extract Gel on Postoperative Fibrotomy Wound Improve Mouth

Opening and Wound Healing in Patients With Oral Submucous Fibrosis? J.oral max.surg.july.2015. 1439.e1–

1439.e10

1. Nucleotides –RNA , DNA, ATP

2. Enzymes –

a. Alkaline & acid phosphatase,

b. Glutammic Oxalo-acetic acid

c. Transaminase

d. Glutamic acid

e. Pyruvic acid transaminase

3. Vitamin – Vit E, B1, B6, B12, Pantothenic acid , nicotinic acid, biotin, PABA, Folic acid

4. Steroids – 17 ketosteroids

5. Cholesterol ,

6. Amino acids,

7. Fatty acids &

8. Trace elements. Zn,Sn, Mg

Placental extracts contains

Placental extract

Available in 4 formsAqueous solution of human placentaLipoid extractsImmuno-gamma globulinsTissue coagulants

Thakur.G et al.Does Topical Application of Placental Extract Gel on Postoperative Fibrotomy Wound Improve Mouth Opening and Wound Healing in Patients With Oral Submucous Fibrosis? J.oral

max.surg.july.2015. 1439.e1–1439.e10

DOSE

• 2 ml of solution deposited at interval of 3 days for in divided region.

• This course can be repeated after a month if required.

(Kakar et al, 1985),

(Gupta and Sharma, 1988),

(Katharia et al,1992),

(Rananjaneyulu and Rao, 1980),

(Gupta et al, 1992)

• 4mg dexamethasone bi weekly

• 1500 IU of hyaluronidase with 1cc of lignocaine bi weekly

• 4mg of dexamethasone and 1500 IU of hyaluronidase

• 2cc Placentrex biweekly

Karkarpuri et al (1985)

• injection of hyaluronidase 1.5 cc for one group and 2cc Placentrex once a week for the other group for 12 consequent weeks, they reported failure rate of 7.2% for hyaluronidase and 31.3% for Placentrex and concluded that hyaluronidase is superior.

Sinha and Jain(1978)

• 2cc of Placentrex intralesionally a week for 10weekswas superior to cortisone

Ramananeyulu and Prabhakar Rao (1980)

Concluded that number 3 combination for seven weeks could give maximum improvement if it is followed by three weeks of hyaluronidase.

Placental extract

Biogenic stimulation

PLACENTAL EXTRACT

Proteolytic enzymes

• Collagenase

• Hyaluronidase

COLLAGENASE

The collagenase treatment not only resulted in a significant

improvement of oral opening, but patients also experienced a

striking reduction in hypersensitivity to spices, sour, cold,

and heat which helped restore eating function.

Sub-mucosal fibrous proliferation, persistently good

vascularization, and a mild increase in thickness of the sub-

mucosal fibrous tissues were noticed 10 months after

collagenase treatment.Dose- 1ml of collagenase(1% solution)

Lin HJ, Lin JC (2007).

Biogenic stimulation

PLACENTAL EXTRACT

Proteolytic enzymes

• Collagenase

• Hyaluronidase

HYALURONIDASE

(HYALASE)

Mechanism

Fibrinolytic enzyme

It helps in breakdown hyaluronic

acid

Lower viscosity of

the intercellular

cement substance

Decreases collagen

formation

DOSE

Intralesionalinjection of Hyalaseused in the dose of 1500 IU

Singh et al.Efficacy of hydrocortisone acetate/hyaluronidase vs triamcinolone acetonide/hyaluronidase in the treatment of oral submucous fibrosis Indian J Med Res

131, May 2010, pp 665-669.

It is recommended that triamcinolone acetonide (10 mg/ml) combined with 1500 IU of hyaluronidase should be given intralesionally particularly in retromolar trigone area half dose each side at 15 days interval for a total of 11 injections in 22 wk.

IMMUNE MODULATION

Topical

Betamethasone

Triamcinolone acetonide

Intralesional

Chymotrypsin

Interferon gamma (IFN-γ)

Hydrocortisone

Betamethasone

Methylprednisolone

Triamcinolone diacetate

Dexamethasone

Systemic

Levamisole

Immune milk

Colchine

Immuno-modulatory drugs

Corticosteroids

Topical•Triamcinalone acetonide 0.1% (Kenacort)

•Betamethasone – 0.5% (Betnesol)

Intralesional•Dexamethasone –4mg/ml (inj Dexona)

•Triamcinolone -40 mg/ml (inj Kenacort)

•Hydrocortisone – 25 mg/ml (inj Wycort)

MECHANISM

• Opposes the action of soluble factors released by

sensitized lymphocytes following activation by specific

antigens.

• Prevent or suppress inflammatory reactions, thereby

preventing fibrosis by decreasing fibroblastic

proliferation and deposition of collagen.

• The initial symptomatic relief could be due to the anti

inflammatory action of the steroids, which helps in

clearing the juxtaepithelial inflammationThough rare, long term intra lesionalinjection of steroid has side effects Osteoporosis, myopathies, peptic ulcer or central serous chorioretinopathy.

Glucocorticoids

Short acting drugs - hydrocortisone,

Intermediate acting drugs - Triamcinolone

Long acting drugs - betamethasone and dexamenthasone.

IMMUNE MODULATION

Chymotrypsin, an endopeptidase, hydrolyzes ester and peptide bonds,

thus acting as a proteolytic and anti-inflammatory agent.

Successful treatment of oral submucous fibrosis with local injections of

chymotrypsin, hyaluronidase, and dexamethasone is reported.

CHYMOTRYPSINIMMUNE MODULATION

Kerr AR et al. A systematic review of medical interventions for oral submucous fibrosis and future research opportunities. Oral Diseases (2011) 17 (Suppl. 1), 42–57.

INTERFERON GAMMA

Downregulates fibroblast proliferation and collagen synthesis

Upregulates the anti-fibrotic cytokines and collagenase synthesis in

the basal layer of epithelium and lamina propria.

Doses-• Intralesional injection of interferon gamma (0.01– 10.0 U/mL) 3 times a day for 6

months(Auluck et al, 2008)

•15 injections of 5o µg (0.25ml) twicw a week ver 8 week(Haque Mf et al 2001)

IMMUNE MODULATION

Haque et al.Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis. J Oral Pathol Med. 2001;30(1):12-21.

LEVAMISOLE

Anthelminthic and Immunomodulator

50 mg three times daily for three alternate weeks

Levamisole can bring about clinical improvement and is better than

antoxid and the combination regimen.

Jirge V, et al 2008

IMMUNE MODULATION

Jirge V, Shashikanth MC, Ali IM, Nisheeth A. Levamisole and antioxidants in the management of oral submucous fibrosis: A comparative study. J Indian Acad Oral Med

Radiol. 2008;20:135–40.

Balaji rao et al. levamisole 150 mg-once daily for 3 days in a week for 6-8 weeks

Immune milk is a kind of skimmed

milk produced from cows immunised

with multiple human intestinal

bacteria.

It has good anti-inflammatory effect

& contains moderate amounts of Vit. A, C, B1, B2, B6, B12, nicotinic acid, pantothenic

acid, folic acid, iron, copper & zinc.

Though chemically its identical to

commercial milk but it contains 20-

30% higher concentration of

IgG type 1 antibody.

45 g of immune milk powder twice daily

for 3 months

(Tai YS, et al 2001)

Immune milk

Tai YS.et al Oral administration of milk from cows immunized with human intestinal bacteria leads to significant improvements of symptoms and signs in patients with oral submucous fibrosis. J Oral Pathol

Med.2001 Nov;30(10):618-25.

1. Pentoxifylline

2. Nylidrin hydrochloride

Promotion of blood flow

1. Pentoxifylline

2. Nylidrin hydrochloride

Promotion of blood flow

Actions • Improves microcirculation • Decreases platelet aggregation as well as granulocyte adhesion. • Inhibits neutrophil adhesion and activation. • Antithrombin, Antiplasmin activities • Fibrinolytic activity (main action for OSMF)• Decrease production of tumor necrosis factor alpha • Reduce some of the systemic toxicities mediated by interleukin-2• Increase the production of PGE2 and PGI2 by

vascular epithelium, maintains cellular integrity

DOSESPentoxifylline : 400 mg 3 times a day

for 7 months

Nylidrinhydrochloride 6mg

Trade name: ARLIDINE

Side effect-• GIT- Nausea, vomiting,• CNS-Dizziness, Headache

Sharma JK et al. 1987

Rajendran R, Rani V, Shaikh S. Pentoxifylline therapy : A new adjunct in the treatment of oral submucous fibrosis. Indian J Dent Res [ 2013];17:190-8.

Betel quid chewing habit

Chronic inflammatory process

TGF-

Collagen production

1. Anti-inflammatory / immuno-modulatory drugs

2. Anti-TGF-

Collagen degradation

PNP PCP

LOX

3. Copper chelators TIMP

Plasminogen activator system

4. Anti-LOX drugs

5. Collagenase activators

Collagenase

The most commonly used combination:

Chymotrypsin (5000 IU),

Hyaluronidase (1500 IU)

dexamethasone (4 mg)

Physiotherapy

Vitamins 50000-100000 IU

Twice weekly submucosal injections for 10 weeks to get satisfactory results

Steroid, vitamins, minerals and enzymes

Hyaluronidase and steroids

Chymotrypsin and steroids

Enzymes, chymotrypsin and steroids

Placental extracts and steroids

Steroids, peripheral vasodilator, vitamins and enzymes

Levamisole and vitamin A

Steroids and antihistaminics

COMBINATIONS

COMBINATIONS

OSMF with trismus be treated by 1.5 ml (37.5 mg) hydrocortisone acetate mixed with 1500IU of hyaluronidase injection given intralesionally half dose on each side at weekly intervalfor 22 wk

Kinger A et al 2004

Triamcinolone acetonide (10 mg/ml) combined with hyaluronidase (1500 IU) intralesionallyonce in 15 days for a total of 11 injections.

Singh M et al2010

Combination of Dexamethasone, Hyaluronidase and Placental extract gives better resultsthan with a single drug.Dose

2 ml of solution deposited at interval of 3 days for in divided region.This course can be repeated after a month if required.

MANAGEMENT

Preventive measures

Medical treatment

Physical therapy

Surgical treatment

Laser

Muscle stretching exercises

Diathermy

Ultrasound

Physical therapy

Muscle stretching exercises for the mouth includes forceful mouth opening with the

help of sticks, ballooning of mouth, hot water gargling.

Forceful mouth opening have been tried with mouth gag & acrylic surgical screw.

Physiotherapy can improve oral opening but not affective to reduce pain –

Cox et al 2009

Muscle stretching exercises Physical therapy

Vijayavel. T, Ponni V. management for oral submucous fibrosis – A comprehensive review. Indian Journal of Multidisciplinary Dentistry. 2014; 4(1): 869-874.

A man diagnosed with OSMF (mouth opening at interincisallevel: 34 mm), was treated with the MED ,followed every month for next 6 months, after which the patient’s mouth opening was improved to 41 mm.

Patil PG , Patil SP. Novel Mouth-Exercising Device for Oral Submucous Fibrosis. Journal of Prosthodontics 21 (2012) 556–560.

Physical therapyMuscle stretching exercises

Diathermy

Low current of 2450 cycles x 20 watts is given.

The mechanism involved is Physiofibrinolysis.

Effective, if it is combined with other treatment modalities.

Advised in early mild and moderate advanced stages of OSMF

selective heating of juxta epithelial connective tissue is possible, thereby limiting the area treated

Physical therapy

Gupta et al 1980

Gupta D, Sharma SC. Oral submucous fibrosis- A new treatment regimen. Oral Maxillofac Surg. 1988; 46: 830-833.

The ErCr:YSGG (waterlase C-100) laser was used to release the fibrotic bands of OSMF that were causing limited

mouth opening.

It works on "hydro-photonic process" in which the laser

energy from the ErCr:YSGG is able to interact with water droplets at tissue to create water molecule excitation. This, in turn, causes water

droplet micro-expansion and propulsion that gives clean and

precise hard-tissue cut.

Analgesics,anti-inflammatory and muscle –relaxing effect.

Lasers

Vijayavel. T, Ponni V. management for oral submucous fibrosis – A comprehensive review. Indian Journal of Multidisciplinary Dentistry. 2014; 4(1): 869-874.

Physical therapy

Ultrasound treatment accelerate healing, increase the extensibility of collagen fibers, provide pain relief and selectively raises the temperature in some well circumscribed areas.

Ultrasound of dose ranging from 0.6 to 2.0 W/Cm2 pulsed 1:1 or 1:2 ( 50% or 33.3 % duty cycle), Frequency of 3 MHz, 5cm diameter transducer head for 3 to 4 minutes to each side over the cheek for 15 consecutive days with permissible one day off each week.

Vijayakumar M, Priya D. Physiotherapy for improving mouth opening & tongue protrution in patients with Oral Submucous Fibrosis (OSMF) – Case Series. International Journal of Pharmaceutical Science and

Health Care. 2013;2(3): 50-58.

Ultrasound used for therapeutic purpose has a frequency of about 0.8-1 MHz and an intensity of 0.5-3 w/cm2.

• During ultrasound therapy, cell

membrane permeability is increased

by altering sodium and potassium

ion gradients. This increased

permeability improves gas exchange

and promotes healing.

• It increases vasodilatation.

• accelerates lymph flow

• decreases inflammation and

stimulates metabolism

Ultrasound therapyPhysical therapy

MANAGEMENT

Preventive measures

Medical treatment

Physical therapy

Surgical treatment

Motawetz G.1987.-Excision of fibrotic

bands with sub-mucosal placements of human skin grafts.

Gupta and sharma et al 1988. Excision of fibrotic bands with

sub-mucosal placements of human

placental grafts.

Khanna and Andrade 1996-in advanced

cases bilateral temporal

myotomy,bilateralcoronoidectomy and palatal island flap.

Surgical treatment

Khanna JN, Andrade NN. Oral submucous fibrosis: a new concept in surgical management—report of 100 cases. Int J Oral

Maxillofac Surg 1995;24(6):433-439.

Surgical striping of fibrous bands

Partial thickness skin or mucosal grafts

Buccal pad of fat interposition

Myotomy

Bilateral temporalis

Temporalis

Nasolabial flap

Palatal island flaps

Lasers- diode and KTP-532 laser

Khanna JN, Andrade NN. Oral submucous

fibrosis: a new concept in surgical management—

report of 100 cases. Int J Oral Maxillofac Surg

1995;24(6):433-439.

Surgical treatment

MALIGNANT

POTENTIAL

Malignant Potential

Paymester –first person to see malignant changes in OSMF

Pindborg JJ et al (1984) : 4.5%

Murti PR et al (1985) : 4.5% to 7.6%

Cox SC, Walker DM (1996) : noted a prevalence of squamous cell carcinoma in 1/3rd of his patients.

Dayal 2000- 13.33 %SCC in OSMF group with trauma

Pindborg JJ (1972) summarized a criteria to support the precancerous nature of this disease as :

Higher prevalence of leukoplakia among submucous fibrosis patients.

High frequency of epithelial dysplasia.

Concurrent findings of submucous fibrosis in oral cancer patients.

Histological diagnosis of oral cancer without clinical suspicion, among submucous fibrosis cases.

Higher incidence of oral cancer among patients with submucous fibrosis.

Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S. Oral submucous fibrosis: Review on etiology and pathogenesis. Oral Oncol.2006;42:561-8

Hyperkeratosis

intercellular edema in the prickle

cell layers and the basal cells

Hyperplasia

Excessive fibrosis Ischaemia

Carcinoma

vulnerability of action of

Carcinogens

irritation by Exogenous

factors

Atrophy of epithelium

Malignant Potential

Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S. Oral submucous fibrosis: Review on etiology and pathogenesis. Oral Oncol.2006;42:561-8

PROGNOSIS

Oral submucous Fibrosis being an irreversible condition has no

effective treatment. Early diagnosis, and treatment and elimination of

the betel nut chewing habit may help ameliorate the condition

Prognosis

CONCLUSION

Koneru A, Hunasgi S, Hallikeri K, Surekha R, Nellithady GS, Vanishree M. A systematic review of various treatment modalities for oral submucous fibrosis. J Adv Clin Res Insights 2014;2:64-72.

Conclusion

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