Www.rxdentistry.co.in. (J.J Pindborg and Sirsat 1966) It is an insidious chronic disease affecting any part of the oral cavity and sometimes the pharynx

www.rxdentistry.co.in

(J.J Pindborg and Sirsat 1966)

It is an 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

changes of the lamina propria with epithelial atrophy

leading to stiffness of the oral mucosa and causing

trismus and inability to eat.


DEFINITION

The condition of oro -pharyngeal OSMF of oral

cavity was prevalent even in the days of

Shushrutha (600 B.C).

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.

The features of which suit the symptomatology

of OSMF.


First described among five East African women of Indian

origin under the term Atrophia idiopathica (tropica)

Mucosae Oris by Schwartz 1952

Joshi in 1953 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"


Paymaster (1956) described the pre-cancerous

nature of the condition.

Other names that have been suggested are:

• Diffuse oral sub-mucous fibrosis (Lal D.1953)

• Sclerosing stomatitis (Behl 1962)

Idiopathic palatal fibrosis (Rao 1962)


OSMF is a crippling fibrotic disorder seen commonly

in India and Indian subcontinent. Sporadic cases are

seen in Malaysia, Nepal, Thailand and South Vietnam.

Incidence of OSMF in India is 0.2-0.5% of population.

Persons between 20 and 40 years of age are most

commonly affected ,but ages have ranged from 2 to 89

years of age

No cast or religious community is especially affected


Case reports also include occurrence of

this condition in a 4 yr old Indian

immigrant girl in Canada, who had been

chewing arecanut since the age of 2 yrs.

Prevalence rate in India ranges from 0.2

to 1.2%www.rxdentistry.co.in


Etiology of OSMF: Exact etiology is unknown. The suggested

factors are,1. Chronic Irritation

Chilies Lime Betel nut Tobacco Chewing2. Deficiency disease.3. Defective iron metabolism4. Bacterial Infection5. Collagen disorder6. Immunological disorders7. Genetic disorder.


Chronic irritation:

Pathogenesis of OSMF lies in the continuous

action of mild irritants.

Chillies:

"Capsaicin" a active extract from capsicum.

The active principle irritant of chillies

(Capsicum annum and Capsicum frutescence)

.www.rxdentistry.co.in

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 and

presence of sub epithelial vesicles

suggested an allergic nature of this disease possibly

due to chilli intake.


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 www.rxdentistry.co.in

Lime:

Betel nut & lime mixture is used for chewing. This

also contains arecoline, lime and tannic acid, 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


Tobacco Chewing

It is a known irritant and a causative factor in oral

malignancies

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


Betel nut:

Considered to be one of important etiological

factor for OSMF

In India arecanut is chewed by itself or in the

form of various areca nut preparations such as

supari, mawa , manipuri , pan masala and in

betel quid either with or without tobacco


The factors that contribute to the pathogenesis in

habitual betel nut chewers.

1. The amount of tannic acid (14-18%)

contained in the betel nut.

2. The influence of mixed calcium powder.

3. Action of arecoline contained in the betel nut

affecting the vascular nerve of oral mucosa and

causing neurotropic disorder


Arecanut contain different type of alkaloids-

arecoline, arecadine, guvacoline, guvacine and

isoguvacine.

Nitrosation of arecoline leads to the formation of

arecanut specific nitrasamine. All arecanut specific

nitrosamines are found to be powerful carcinogens

and alkylate DNA.


KHANNA AND ANDHARA , have suggested pathogenesis

of OSMF by dual action of arecanut. They suggested that ,

Arecoline , stimulate fibroblastic proliferation and collagen

synthesis.

The flavonoids catechin and tannins stabilize the collagen

fibrils rendering them resistant to degradation by

collagenase.

The attendent trismus is a result of juxtaepithelial

hyalinization and secondary muscle involvement (i.e.

muscular degradation and fibrosis)

The habit of chewing areca nut leads to muscle fatigue


Vitamin B12 and Iron deficiency are

associated with OSMF. The deficiency

could be due to the fact that defective

nutrition due to impaired food intake in

advanced cases of OSMF, may be the

effect rather than the cause of the disease


Impaired cellular utilization of iron explains the

presence of hypochromic microcytic anemia.

There is no definite proof to support the

hypothesis that defective iron utilization by oral

mucosa and sub-mucosa is the cause of OSMF


Mukherjee and Biswas (1972) suggested

that there is:

Rise in mucoprotein and

mucopolysaccharide level

Rise in anti-streptolysin - O titre in OSMF

patients.

(But these works are not confirmed)


Collagen disorder:

Rao (1962) suggested that OSMF is a

localized condition of collagen disease.

He linked it to scleroderma, rheumatoid

arthritis, duputreyens contracture and

intestinal fibrosis. Histological features

were found to be similar in OSMF and

scleroderma.


HARMONAL FACTORS

There would appear to be predisposition

in female with a ratio of women to men of

3:1

(Pillai R et al “pathogenesis of Oral

submucous fibrosis”, cancer

1992 ;69:2011-2017)


IMMUNOLOGICAL DISORDER:

Oral Submucous fibrosis is a high risk pre-

cancerous condition. Raised ESR and globulin

levels are found, indicative of immune

inflammatory disorder.

Serum immunoglobulin levels IgA, IgG and IgM

levels are raised. These suggest an antigenic

stimulus in absence of any infection.

Increased circulating immune complex in OSMF


Genetic predisposition to the disease ,

involving the HLA

antigens ,A10,DR3,DR7and probably B7

and the haplotypic pairs A10/DR3 and

A10/B8 has been demonstrated.


The increased evidence of CD4 and HLA-DR-positive

cells and high ratio of CD4 to CD8 in OSF tissue suggest

an ongoing cellular immune response leading to

imbalance of immunoregulation and alteration in local

tissue architecture.


Mast cells

Mast cells are characterized by numerous cytoplasmic

granules. Its cytoplasm contains

mucopolysaccharides, histamine and heparin.

Many patients with early stage of OSMF give history of

feeling of itching sensation which could be due to

release of histamine exact role of mast cells in

inflammation is not known.


MULTIFACTORIAL PATHOGENESIS


ARECANUT TOBACCO LIME VOLATILE OILSVOLATILE LIQUIDS

TANNIN& AFLOTOXIN

ARECOLINE

DEGRADATIONOF COLLAGEN

INCREASED SYNTHESIS OF COLLAGEN

MECHANICAL TRAUMA

CHEMICAL BURN HYPERSENSITIVITY

ALTERED IMMUNITYGENETIC

REDISPOSITION

FIBROBLAST FORMATION

IRREVERSIBLE FIBROSIS

CACINOMAEXPOSURE CONTINOUS

Brief review : pathogenesis of OSMF

Section of fibroblasts with a high amount of

collagen production during long term exposure

to arecanut ingredients.

Stimulation of fibroblast proliferation and

collagen synthesis by arecanut alkaloids or by

fibrogenic cytokines secreted by activated

macrophages and T lymphocytes in the OSF

tissuewww.rxdentistry.co.in

Decreased secretion of collagenase and

deficiency in collagen phagocytosis by OSF

fibroblasts

Production of collagen with a more stable

structure (collagen type I trimer) by OSF

fibroblast.

Stabilization of collagen structure by catechin

and tannin from arecanut and an increase in

collagen cross linkage caused by up regulation

of lysy oxidase by OSF fibroblastwww.rxdentistry.co.in

Malignant transformation rate is 7.6%

(JIAOM, vol-iv;no.3& 4 July-Dec.1993, p 12-15)


The data regarding the sex predilection is conflicting. Earlier it was thought to be common in females.

But at present ,study ratio shows 2.3: 1 =M:F

Age group common is 2 to 3rd decade of life

But cases have been reported from 4 year to 86 yrs


Prodromal symptoms : Onset is insidious. The most common

initial symptoms are: Burning sensation on eating spicy food Blisters on the palate Ulceration or recurrent stomatitis Excessive salivation Defective gustatory sensation Dryness of mouth.


Later, Difficulty in opening mouth

Inability to whistle, blow

Difficulty in swallowing

When fibrosis involves pharynx- referred pain to

the ear.

Changes in tone of the voice due to vocal cord

involvement

Some times deafness due to occlusion of

eustachian tubes


COMMON SITES INVOLVED

Buccal mucosa, faucial pillars ,soft palate, lips

and hard palate.

The fibrous bands in the buccal mucosa run in a

vertical direction ,sometimes so marked that

the cheeks are almost immovable.

In the soft palate the fibrous bands radiate from

the pterygomandibular raphe or the faucial

pillars and have a sear like appearancewww.rxdentistry.co.in

The uvula is markedly involved , shrinks and

appears as a small fibrous bud.

The faucial pillars become thick , short, and

extremely hard.

The tonsils may be pressed between the

fibrosed pillars

The lips are often affected and upon

palpation , a circular band can be felt around

the entire rima oris

When gingiva is affected , it is fibrotic,

blanched and devoid of its normal stippled

appearance. www.rxdentistry.co.in








Clinically signs of OSMF can be grouped as:

Stage I : Stage of stomatitis &

vesiculation

Stage ll : Stage of fibrosis

Stage III : Stage of sequelae

complication


Stage of stomatitis & vesiculation

It is earliest stage and characterized by

recurrent stomatitis and vesiculation. Patient

complaints of burning sensation in the mouth &

inability to eat spicy food.

On examination vesicles on palate are seen.

They rupture and form superficial ulcers.

Some amount of fibrosis is also present.


Stage ll: Stage of fibrosis There is inability to open mouth completely

and stiffness in mastication. As disease advances there is difficulty in blowing out cheek & protruding tongue. Sometimes pain in ear and speech is muffled.On examination there in increasing amount of fibrosis in the submucosa. This causes blanching of mucosa.

Lips & checks become stiff & loose their normal resistance. Shortening & disappearance of uvula in advanced cases.

Dorsum of tongue shows atrophy of papillae. Mucosa of floor of mouth show blanching &

stiffness


Stage of sequelae & Complication

Patient presents with all the complaints as in

stage II. Also there may be evidence of

leukoplakia.

Changes in mucosa are whitish or brownish

black-

Pindborg et al (1967) found the OSMF was

found in 40%cases of oral cancer than in

general population 1.2%.



GRADE-I

Incipient

(very early stage)

GRADE-II

Mild

(early stage)

GRADE-III

Moderate

Moderately advanced stage

GRADE-IV

severe advanced

stage

1.Burning sensation,

dryness of mouth, vesicles or ulceration

1.Burning sensation, dryness of

mouth

1.Burning sensation, dryness of mouth

1.Burning sensation, dryness of

mouth

2.Irritation with

spicy food

2.Irritation with

spicy food

2.Irritation with

spicy food

2.Irritation with

spicy food

3.No change in mucosal colour

3. Oral mucosa is blanched and loses its elasticity

3.Blanched ,opaque, leather like

mucosa

3.Blanched ,opaque, leather like mucosa

4. No fibrous bands

4. No clear cut fibrotic bands

4. Vertical fibrotic bands on buccal mucosa making it stiff

4. Thick fibrous bands occurring on both buccal mucosa, in retromolar area and at ptrygomandibular raphe

5. Mouth opening normal

5. Slight restriction of mouth opening

5.Considerable restriction of mouth opening

5. Very little mouth opening


6.Tongue protrussion normal

6.Tongue protrussion normal

6. Tongue protrussion not much affected

6.Restricted tongue protrussion

7.Difficulty in eating and speaking

7. Speech and eating very much impaired

8.Oral hygiene poor

8.Oral hygiene very poor


DIAGNOSIS IS BASED ON :

Clinically discernible blanching and pallor

Palpable bands and restriction-of mouth opening.

Severe burning sensation of mouth, aggravated

by use of even moderate spicy food.

Biopsy report characteristically showing

histopathologically


Atrophic Oral epithelium.

Loss of rete pegs .

Epithelial atypia may be observed.

Hyalinization of collagen bundles.

Fibroblasts decreased and blood

vessels obliterated.


Stage 1: Early OSMF Mild blanching. No restriction in mouth opening .Central

incisor tip Males... 35-45mm to tip of same side. Females 30-42mm.

No restriction in tongue protrusion .Mesio incisal angle of upper central incisor to the tip of the tongue when maximally extended with mouth wide open-Males 5-6 cms and Females 4.5-5.5 cms.


Stage 2 : Moderate OSMF…

Moderate to severe blanching .

Mouth opening reduced by 33%.Flexibility also

demonstrably decreased.

Burning sensation even in absence of stimuli.

Palpable bands felt.

Lymphadenopathy either unilateral or bilateral.

Demonstrable anemia on hematological

examination.


Stage 3: Severe OSMF Burning sensation very severe. patient

unable to do day to day work. More than 66% reduction in the mouth

opening cheek flexibility and tongue protrusion, the tongue may appear fixed.

Ulcerative lesions may appear on the cheek.

Thick palpable bands. Lymphadenopathy bilaterally evident..



Lab findings reflect the nature of tissue

changes in this condition rather than

any diagnostic importance.

Increased ESR

Anemia

High eosinophil count

Hyper gammaglobulinaemia

Lower serum vitamin A levels



MANAGEMENT Various modalities of treatment have

been tried.

1.Restriction of habits/ Behavioral therapy

2. Medicinal therapy

3. Surgical therapy.

4. Oral Physiotherapy


Restriction of habits/behavioral therapy

The consumption of pan, betel nut, chillies, spices,

& commercially available, pan masalas, guthkas

with or without tobacco is increasing in India. So

people should be encouraged to stop these habits

Affected patients should be explained about the

disease and possible malignant potential of OSMF.

Possible irritants should be removed

Nutritional supplements.


MEDICINAL THERAPY

Antioxidants

Intralesional injections of hyaluronidase.

Use of Placentrix 2ml solution at interval

of 3 days in five divided region

Topical application of 4% Acetic acid

(variable) 3 times daily.


Topical application of immunomodulators:

5 Fluorouracil

Systemic administration of immunomodulators

Levamisole 150mg for 3 weeks

Dapsone 75 mg O.D for 90 days


SURGICAL TREATMENT

Fibrotomy

Cryosurgery

Laser treatment



Documents

Www.rxdentistry.co.in. (J.J Pindborg and Sirsat 1966) It is an insidious chronic disease affecting any part of the oral cavity and sometimes the pharynx