4. 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
5. 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
6. 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.
7. 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.
8. 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 malignant
transformation
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
9. Group III: Inherited disorders that do not
necessarily alter the clinical appearance of
local tissue but are associated with a greater
than normal risk of PMD or malignant
transformation.
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
11. 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.
12. “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.
13. “ 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.
15. 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.
16. 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
20. 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%
23. Etiopathogenesis
Capsicum
annum &
capsicum
frutescence
Active extract :
Capsaicin
Vanillylamide
of 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 siderophenic
dysphagia 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.
24. 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 = English
That Tha or Kun Ja = Myanmar (Burma)
Supadi = Nepalese
Supari = Hindi, Bengali
Adike = Kannada
Mak or Mahk = Thai
Pinlang, Pinang = China & Sarawak
India:
o Paan , Paan-Gutkha
o Paan masala (dry form, no tobacco)
o Gutkha
o 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’ is
derived from the Malay word
adakka (areca nut) or from
adakeya, the Indian
equivalent
26. 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
27. 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
30. 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
31. Smokeless tobacco
KHAINI
Powdered sun-dried tobacco, slaked
lime (CaOH2) paste mixture
occasionally used with areca nut.
Placed in mouth/ chewed.
Commonly used - Maharashtra
35. 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.
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
37. 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.
38. 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.
40. 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.
41. 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.
42. 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
43. BMP- Bone
Morphogenic Protein
PCP- Pro Collagen C
Proteinase
LOX- 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.
44. 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.
45. 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.
46. Pathogenesis
Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.
47. Pathogenesis
Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.
48. 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.
49. 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.
50. 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
Plasma
Fibrinogen
Altered immunity
Pathogenesis
Chaturvedi VN, Sharma AK, Chakrabarati S. Salivary coagulopathy and humoral response in oral
submucous fibrosis. JIDA 1991;62:51- 9.
52. 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
55. Clinical features
Bud shaped uvula
Restricted tongue movement
Hockey stick appearance of uvula
Depapilated tongue Associated with premalignancy
56. 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
58. 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
59. 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.
60. 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
61. 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
62. 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.
63. 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.
64. 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
65. 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.
66. 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.
67. 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.
68. 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.
69. 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.
70. 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.
71. 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.
72. Classification based on clinical features of OSMF
Chandramani More et al (2011)
M1
• Interincisal
mouth
opening up
to or
greater
than 35
mm.
M2
• Interincisal
mouth
opening
between
25 and 35
mm
M3
• Interincisal
mouth
opening
between
15 and 25
mm
M4
• Interincisal
mouth
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.
73. 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
74. 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 polymorphonuclear
leukocytes 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.
75. 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.
77. 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.
79. 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
82. 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.
83. 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
84. Diagnosis
Assessment 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.
87. 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
88. 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
89. 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
97. b-carotene, vitamins A, C and E, zinc
Lycopene
Curcumins
Oxitared capsule
Nutrients, Micronutrients and Anti-oxidants
98. 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
99. Kelkel M et al. Antioxidant & antiproliferative propertiesv of lycopene. Free radical research, 2011;45(8):925-940.
The antioxidant potential
has been ranked as follows
lycopene > α-tocopherol >
α-carotene > ß-
cryptoxanthin > zeaxanthin
= ß-carotene > lutein
ANTIOXIDANTS
100. 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
101. 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
102. 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
103. 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
105. 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 Acid
ANTIOXIDANTS
106. b-carotene, vitamins A, C and E, zinc
Lycopene
Curcumins
Oxitared capsule
Nutrients, Micronutrients and Anti-oxidants
Antioxidants
107. 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,highly
unsaturated 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
108. Agarwal A,Roa A .Tomato lycopene and its role in human health & chronic diseases . CMAJ.2009;163(6)
Lycopene
109. 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
Caratenoids
10.33 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
MCG
Lycopene 5 MG
Vitamin E 10 IU
Zinc sulphate
27.45 MG
Lycopene 15 mg
Zinc 5 mg
Vitamin C 40
mg Vitamin D
20 mcg
110. b-carotene, vitamins A, C and E, zinc, copper, manganese and
selenium
Lycopene
Curcumins
Spirulina
Oxitared capsule
Nutrients, Micronutrients and Anti-oxidants
ANTIOXIDANTS
111. 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-2011
Significant improvement was observed in the clinical sign, symptoms and even
histopathologically.
112. Antioxidants (b-carotene, vitamins A, C and E,
zinc, copper, manganese and selenium)
Lycopene
Curcumins
Oxitared capsule
Nutrients, Micronutrients and Anti-oxidants
116. Placental extract
Placentrex was first introduced By Flator(1933) and later developed
in 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 when
severed from the parent body and exposed
to a condition unfavorable, undergo
biological re-adjustments leading to the
development of substances in state of
their survival to ensure their vitality as
BIOGENIC STIMULATORs.
Such tissues or their extracts when
implanted or injected into the body after
resistance to pathogenic factors
stimulates metabolic or regenerative
process 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
117. 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 forms
Aqueous solution of
human placenta
Lipoid extracts
Immuno-gamma globulins
Tissue 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
118. 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
120. 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).
122. HYALURONIDASE
(HYALASE)
Mechanism
Fibrinolytic
enzyme
It helps in
breakdown
hyaluronic
acid
Lower
viscosity of
the
intercellular
cement
substance
Decreases
collagen
formation
DOSE
Intralesional
injection of Hyalase
used 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.
124. 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 inflammation
Though rare, long
term intra lesional
injection 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
125. 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.
CHYMOTRYPSIN
IMMUNE 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.
126. 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.
127. 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
128. 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.
130. 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
DOSES
Pentoxifylline : 400
mg 3 times a day
for 7 months
Nylidrin
hydrochloride 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.
131. 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
132. 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
133. COMBINATIONS
OSMF with trismus be treated by 1.5 ml (37.5 mg) hydrocortisone acetate mixed with 1500
IU of hyaluronidase injection given intralesionally half dose on each side at weekly interval
for 22 wk
Kinger A et al 2004
Triamcinolone acetonide (10 mg/ml) combined with hyaluronidase (1500 IU) intralesionally
once in 15 days for a total of 11 injections.
Singh M et al2010
Combination of Dexamethasone, Hyaluronidase and Placental extract gives better results
than 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.
136. 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.
137. A man diagnosed with OSMF
(mouth opening at interincisal
level: 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
138. 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.
139. 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
140. 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 therapy
Physical therapy
142. 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,bilateral
coronoidectomy 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.
143. 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
145. 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
146. 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
148. 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
151. Koneru A, Hunasgi S, Hallikeri K, Surekha R, Nellithady GS, Vanishree M. A systematic review of various treatment
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Conclusion
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One such reaction of the collagen of oral mucosa to arecanut is ORAL SUBMUCOUS FIBROSIS
OSMF is characterized by deposition of dense collagen in the connective tissue
The current Working Group of WHO (2005) does not favor subdividing precancer to lesions
and conditions and the consensus view was to refer to all clinical presentations that carry a
risk of cancer under the term ‘oral potentially malignant disorders’ (OPMD) to reflect their
widespread anatomical distribution
disorder’ is defined as ‘a disturbance of normal functioning of the mind
or body caused by genetics, disease or trauma. Hence, the word ‘disorders’ used in the
proposed definition appears apt over the words ‘lesions’ and ‘conditions’. The word ‘disease’
instead of ‘disorder’ will be inappropriate because patient having ‘precancer’ may not
necessarily be diseased (ill, sick or symptomatic).
The condition of oro -pharyngeal OSMF of oral cavity was prevalent even in the days of Shushrutha (600 B.C).
Capsaicin" a active extract from capsicum is the active principle irritant of chillies.
The use of chillies (Capsicum annum and Capsicum frutescence) play an etiological role in OSMF
Capsaicin, which is “vanillylamide of 8-methyl-6-nonenic acid”, is the active ingredient of chillies, play an etiological role in oral submucous fibrosis
Areca nut constitutes of alkaloids, flavonoids and other trace elements like copper (Figure 3). The major alkaloids found in areca nut are arecoline, arecaidine, guvacine, guvacoline which cause fibroblastic proliferation and increased collagen formation, of which arecoline and arecaidine are the major causative factor.
Flavonoid component of areca nut have some direct influence on collagen metabolism, enhancing the cross linking of collagen fibers and hence raise the lysyl-oxidase (LOX) activity. The LOX activity is important for formation of insoluble collagen due to cross-linking.
Betel nut & lime mixture is used for chewing.
Tobacco Chewing
It is a known irritant and a causative factor in oral malignancies
Genetic predisposition is also considered- Gene polymorphism of gene encoding for Tumour necrosis factor alpha, Aberrations of other cytokines such as Transforming Growth Factor beta and Interferon gamma, Association with specific Human Leucocyte Antigens such as HLA A10, B7, DR3.
HPV DNA, HSV DNA and EBV DNA were detected from patients with OSMF. A possible role of H pylori in the etiology of mucosal inflammation in OSMF is also found out.
The serum beta carotene level was found to be lower in the patients with OSMF.
May be secondary
The disease is characterized by repeated vesiculations and ulcerations. A subclinical vitamin B complex deficiency has been suspected.
OSMF patients cannot tolerate spicy food & the opening of the mouth in OSF patients becomes smaller which may affect normal food intake and lead to nutritional deficiencies.
No definite proof to support the hypothesis that defective iron utilization by oral mucosa and sub-mucosa is the cause of OSMF
Features which suggest autoimmune nature of osmf-
an antibody produced by an organism in response to a constituent of its own tissues.antinuclear (ANA), antismooth muscle (SMA), antigastric parietal cell (GPCA), antithyroid microsomal (TMA), and antireticulin antibodies
Most studies on pathogenesis have concentrated on changes in extracellular matrix based on the premise that increased collagen synthesis or reduced collagen degradation is the possible mechanism for the development of this disease
Heat shock protein (HSP 47) is a collagen specific molecular chaperone involved in the processing and/or secretion of procollagen. HSP 47 is significantly upregulated in OSF. Arecoline was found to elevate HSP 47 expression in fibroblasts.
Cystatin C, a non glycosylated basic protein is increased in a variety of fibrotic diseases, Cystatin C was found to be upregulated both at m–RNA and protein levels in the disease. Arecoline is responsible for this enhancement in a dose dependent manner
In case of chronic betel quid chewers, there is constant irritation to the oral mucosa.
This will generate an injury related chronic inflammation
Due to chronic inflammation there will be activated T cell & macrophages at the site. Hence there will be an increase in the cytokines and growth factors such as InterLeukin6, Tumour Necrosis Factor alpha, Interferon gamma, Transforming Growth Factor beta.
Transforming Growth Factor (TGF) causes activation of tissue inhibitor of matrix metalloproteinase gene (TIMPs) and activation of plasminogen activator inhibitor gene (PAI).
Flavonoid component of areca nut have some direct influence on collagen metabolism, enhancing the cross linking of collagen fibers
TGF beta causes increased expression of procollagen gene, BMP, PCP.
Due to increased activation of procollagen gene, there is increased levels of procollagene proteinase.
BMP and PCP converts Pro LOX to LOX
Due to Copper content in areca nut there is Increased activity of lysyl oxidase enzyme which stimulates & proliferates Fibroblast. Ie . And converts soluble collagen into insoluble collagen
Flavonoid component of areca nut have direct influence on collagen metabolism, enhancing collagen production
Hydrolysis of arecoline produces arecaidine that has pronounced effects on fibroblasts. The stimulation of fibroblasts is greater with arecaidine, and there was a concentration-dependent stimulation of collagen synthesis when fibroblasts were exposed to both arecloine and arecaidine, addition of slaked lime calcium hydroxide(Ca(OH)2 ) to areca nut in pan facilitates hydrolysis of arecoline to arecaidine making this agent available in the oral environment and hence causing greater stimulation of fibroblast.
Flavonoid component of areca nut have some direct influence on collagen metabolism, enhancing the cross linking of collagen fibers and hence raise the lysyl-oxidase (LOX) activity. The LOX activity is important for formation of insoluble collagen due to cross-linking. The process of cross-linking gives tensile strength and mechanical properties to the fibers as well as makes the collagen fibers resistant to proteolysis. The LOX is an essential enzyme for final processing of collagen fibers into a stabilized covalently cross-linked mature fibrillar form that is resistant to proteolysis.
Buflomedial hydrochloride
Danxuan Koukang (DXKK)
Extensive fibrosis of the connective tissue causes reduction of vascularity, resulting in subsequent hypoxia in both fibroblasts and surface epithelium. Hypoxia causes atrophy and ulceration of the epithelium by inducing apoptosis. Also there is an Overexpression of hypoxia-induced factor-1a is seen in OSMF.
In case of OSMF there is increase in the Serum copper levels and there is a decrease in the Serum iron, zinc and selenium levels.
Saliva has an indirect action. It acts as a vehicle of Fibrin Production Factor which interacts with plasma fibrinogen and causes dense fibrosis.
Studies have shown that there is an increase in Mast Cell Density (MCD) in OSMF patients. And due to this there is an exponential increase in Micro Vascular Density (MVD). This suggests that there is fibrosis taking place
The Frequency of micronucleated cells and micronuclei in OSMF patients were found to be increased and decrease in plasma total cholesterol, HDLC, and triglycerides is seen
As the disease progresses, the oral mucosa becomes blanched and slightly opaque and white fibrous bands appear.
Seen due to impairment of local vascularity as a result of fibrosis
Blanching can be Localized/Diffuse/Reticular(lace like)
Can affect any area of oral cavity but Palate and the faucial pillars are the areas involved first.
Hyper pigmented areas adjacent to zones with loss of pigments can be seen
Prevalence of location of bands Faucial bands > Buccal bands > Labial bands
Soft palate-The density of the fibrous deposit varies from a slight whitish area on the soft palate causing no symptoms to a dense fibrosis causing fixation and shortening or even deviation of the uvula and soft palate
he divided intraoral regions into eight anatomical subregions viz palate, posterior one-third of buccal mucosa, mid one-third of the buccal mucosa, anterior one-third of buccal mucosa, upper labial mucosa, tongue and floor of mouth and looked for disease involvement in each to assess the extent of clinical disease.
opening (normal
distance between central incisor tips: Males 35 to 45 mm, females 30 to 42 mm),
no restriction in tongue protrusion (normal mesioincisal angle of upper central
incisor to the tip of the tongue when maximally extended with the mouth wide open: Males 5 to 6 cm, females 4.5 to 5.5 cm). Cheek flexibility CF = V1-V2, two
points measured between; V2 = is marked at 1/3rd the distance from the angle of
the mouth on a line joining the tragus of the ear and the angle of the mouth and V1
= the subject is then asked to blow his cheeks fully, and the distance measured
between the two points marked on the cheek. Mean value for males = 1.2 cm,
females = 1.08 cm.
Mesio-incial angle of upper central incisor to the tip of the tongue when maximally extended with mouth wide open (Normally Males 6.73cm and Females 6.07cm)
Cheek flexibility, CF= V1-V2. Two points measured between at one third the distance from the angle of the mouth on a line joining the tragus of the ear and the angle of the mouth, the subject is then asked to blow his cheeks fully and the distance measured between the two points marked on the cheek V1. CF =V1-V2.
Mean value for males- 1.2 cm, females- 1.08 cm,
A linear relationship was observed between the mouth opening and age in both males and females and the mouth opening decreased as the age increased.
defective lymphocyte function and hyperactivity of B cells leading to hyperglobulinaemia
There is a direct relationship between serum copper and extent of fibrosis. Serum copper levels are directly proportional to increased clinical stage of OSMF.
carotenodermy
[Abhinav kumar et al, Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:207-13]
Lycopene was seen to be efficacious as a safe, reliable drug in the management of oral submucous fibrosis.
Because of its high number of conjugated dienes, lycopene is one of the most potent antioxidants, with a singlet-oxygen-quenching ability twice as high as that of β-carotene and 10 times higher than that of α- tocopherol
Lycopene is available in the market as mix formulation with some other carotinoids and antioxidants.
Enzymes and vitamins help in regeneration of healthy tisssue.
Steroids restores loss of substances as it contains the epidermal growth producing factor and stimulates immunoglobulin levels of IgG and IgM. It also has anti inflammatory action
Hyaluronidase belongs to the family of enzymes that degrade hyaluronic acid.
It is termed as a “Rheologic modifier.”
Some of the possible interventions suggested based on the pathway involved include: (1) blocking the chronic inflammatory process by anti-inflammatory/immuno-modulatory drugs; (2) blocking TGF-b action by anti-TGF-b antibodies or peptide mimetics of soluble TGF-b receptors; (3) copper chelators like penicillamine to block LOX activity and prevent cross-linking; (4) other anti-LOX drugs that prevent its action; (5) collagenase activators like colchicine to promote collagen degradation. Probably a combinational therapy of the above mentioned drugs thereby intervening at multiple points along the pathway might be useful for the successful treatment of OSF.
This is thought to put pressure on fibrous bands.
Surgical treatment remains the method of choice at this late and irreversible stage.
The fibrous bands have been surgically excised followed by
The only effective surgical procedure is that of split thickness skin grafting following bilateral temporalis myotomy or coronoidectomy.
LASER - CO2 laser surgery offers advantage in alleviating the functional restriction.