(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.
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
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
In the year 1954, Su. 1. P. from Taiwan described similar
condition, which he called "Idiopathic Scleroderma of
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
Etiology of OSMF:
Exact etiology is unknown. The suggested
1. Chronic Irritation
2. Deficiency disease.
3. Defective iron metabolism
4. Bacterial Infection
5. Collagen disorder
6. Immunological disorders
7. Genetic disorder.
Pathogenesis of OSMF lies in the continuous
action of mild irritants.
"Capsaicin" a active extract from capsicum.
The active principle irritant of chillies
(Capsicum annum and Capsicum frutescence) .
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.
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
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
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
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
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
The flavonoids catechin and tannins stabilize the collagen
fibrils rendering them resistant to degradation by
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
Rise in anti-streptolysin - O titre in OSMF
(But these works are not confirmed)
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
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
Oral Submucous fibrosis is a high risk pre-
cancerous condition. Raised ESR and globulin
levels are found, indicative of immune
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
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.
ARECANUT TOBACCO LIME VOLATILE OILS
MECHANICAL CHEMICAL BURN HYPERSENSITIVITY
DEGRADATION INCREASED SYNTHESIS ALTERED IMMUNITY REDISPOSITION
OF COLLAGEN OF COLLAGEN
EXPOSURE CONTINOUS CACINOMA
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
Decreased secretion of collagenase and
deficiency in collagen phagocytosis by OSF
Production of collagen with a more stable
structure (collagen type I trimer) by OSF
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 fibroblast
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
Age group common is 2 to 3rd decade of
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
Defective gustatory sensation
Dryness of mouth.
Difficulty in opening mouth
Inability to whistle, blow
Difficulty in swallowing
When fibrosis involves pharynx- referred pain to
Changes in tone of the voice due to vocal cord
Some times deafness due to occlusion of
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 appearance
The uvula is markedly involved , shrinks and
appears as a small fibrous bud.
The faucial pillars become thick , short, and
The tonsils may be pressed between the
The lips are often affected and upon palpation ,
a circular band can be felt around the entire
When gingiva is affected , it is fibrotic, blanched
and devoid of its normal stippled appearance.
Clinically signs of OSMF can be grouped as:
Stage I : Stage of stomatitis &
Stage ll : Stage of fibrosis
Stage III : Stage of sequelae
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 &
Stage of sequelae & Complication
Patient presents with all the complaints as in
stage II. Also there may be evidence of
Changes in mucosa are whitish or brownish
Pindborg et al (1967) found the OSMF was found
in 40%cases of oral cancer than in general
GRADE-I GRADE-II GRADE-III GRADE-IV
Incipient Mild Moderate severe
(very early stage) (early stage) Moderately advanced advanced
1.Burning 1.Burning 1.Burning sensation, 1.Burning
sensation, sensation, dryness of mouth sensation,
dryness of mouth, dryness of dryness of
vesicles or mouth mouth
2.Irritation with 2.Irritation 2.Irritation with 2.Irritation
spicy food with spicy food with
spicy food spicy food
3.No change in 3. Oral mucosa 3.Blanched 3.Blanched
mucosal colour is blanched and ,opaque, leather ,opaque, leather
loses its like mucosa like mucosa
4. No fibrous 4. No clear cut 4. Vertical 4. Thick fibrous
bands fibrotic bands fibrotic bands bands occurring
on buccal on both buccal
mucosa making mucosa, in
it stiff retromolar area
5. Mouth opening 5. Slight 5.Considerable 5. Very little
normal restriction of restriction of mouth opening
mouth opening mouth opening
6.Tongue 6.Tongue 6. Tongue 6.Restricted
protrussion protrussion protrussion not tongue
normal normal much affected protrussion
7.Difficulty in 7. Speech and
eating and eating very
speaking much impaired
8.Oral hygiene 8.Oral hygiene
poor very poor
DIAGNOSIS IS BASED ON :
Clinically discernible blanching and pallor
Palpable bands and restriction-of mouth
Severe burning sensation of mouth, aggravated
by use of even moderate spicy food.
Biopsy report characteristically showing
Atrophic Oral epithelium.
Loss of rete pegs .
Epithelial atypia may be observed.
Hyalinization of collagen bundles.
Fibroblasts decreased and blood
Stage 1: Early OSMF
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
Burning sensation even in absence of stimuli.
Palpable bands felt.
Lymphadenopathy either unilateral or bilateral.
Demonstrable anemia on hematological
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
Thick palpable bands.
Lymphadenopathy bilaterally evident..
Lab findings reflect the nature of tissue
changes in this condition rather than any
High eosinophil count
Lower serum vitamin A levels
Various modalities of treatment have been
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
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:
Systemic administration of immunomodulators
Levamisole 150mg for 3 weeks
Dapsone 75 mg O.D for 90 days