oral submucous fibrosis - osmf : dr sanjana ravindra
TRANSCRIPT
CONTENTS
Introduction
History
Definition
Epidemiology
Nomenclature
Etiopathogenesis
Clinical features
Classification
Histopathology
Differential
diagnosis
Diagnostic Criteria
Investigations
Management
Malignant Potential
Prognosis
Conclusion
References
The oral cavity is lined with an
uninterrupted mucosa which is
continuous with the skin near
vermillion border of the lips and with
the pharyngeal mucosa in the region
of soft palate
INTRODUCTION
Inderbir Singh.Textbook of Human Histology 5th edition Jaypee Brothers Medical Publishers;2009
//www.google.co.in/search?q=oral+mucous+membrane
OMM- Unique area of the body, which is
continuously exposed to various kinds of stresses
such as heat, cold, microorganisms, chemicals and
mechanical irritations.
In response to these stresses, both epithelium and connective tissue layers of the oral mucosa exhibit acute and chronic reactive
changes
INTRODUCTION
POTENTIALLY MALIGNANT DISORDERS
INTRODUCTION
PRECANCEROUS LESION
A morphologically altered tissue in which
oral cancer is more likely to occur than in its
apparently normal counterpart
Leukoplakia
Erythroplakia
Mucosal changes associated with smoking
habits
Carcinoma in situ
Bowen’s disease
Actinic keratosis, cheilitis and elastosis
PRECANCEROUS CONDITION
A generalized state associated with a
significantly increased risk of cancer
Oral submucous fibrosis
Syphilis
Sideropenic dysplasia
Oral lichen planus
Dyskeratosis congenita
Lupus erythematosus
World Health Organization. Report of a meeting of investigators on the histological definition of precancerous lesions. Geneva: World Health Organization; 1973 Can 731.
ORAL POTENTIALLY MALIGNANT DISORDERS
INTRODUCTION
“It is a group of disorders of varying etiologies, usually tobacco;
characterized by mutagen associated, spontaneous or hereditary alterations
or mutations in the genetic material of oral epithelial cells with or without
clinical and histomorphological alterations that may lead to oral
squamous cell carcinoma transformation."
Sarode SC, Sarode GS, Tupkari JV. Oral potentially malignant disorders: Precising the definition. Oral Oncol 2012; 48: 759–760.
Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral
mucosa. J Oral Pathol Med 2007; 36: 575– 80.
1. HABIT RELATED
a. Tobacco associated lesions
b. Leukoplakia
c. Tobacco pouch keratosis
d. Stomatitis palatine nicotini
e. Betel nut associated
f. Oral submucous fibrosis
g. Sanguinaria-associated keratosis
2. NON-HABIT RELATED
a. Actinic cheilosis
b. Chronic candidiasis⁄
Group I: Morphologically altered tissue in which external factor is responsible for the etiology and malignant transformation.
Group II: Morphologically altered tissue in which chronici nflammation is responsible for malignanttransformation
IIA. CHRONIC INFLAMMATION CAUSED
BY INTERNAL DERANGEMENT.
1. Lichen planus
2. Discoid lupus erythematosus
IIB: CHRONIC INFLAMMATION CAUSED
BY EXTERNAL FACTORS.
1. Chronic mucosal trauma
2. Lichenoid reactions
3. Poor oral hygiene
4. Chronic infections
a. Chronic bacterial infections
b. Chronic viral infections
c. Chronic fungal infections
5. Other pathologies associated with prolonged
untreated chronic inflammation of the oral
cavity.
New classification of OPMD . Oral oncology head and neck 2011
INTRODUCTION
Group III: Inherited disorders that do notnecessarily alter the clinical appearance oflocal tissue but are associated with a greaterthan normal risk of PMD or malignanttransformation.
1. Inherited cancer syndromes
a. Xeroderma pigmentosum
b. Ataxia telangiectasia
c. Bloom syndrome
d. Fanconi’s anemia
e. Li Fraumeni syndrome
2. Dyskeratosis congenita
3. Epidermolysis bullosa
4. White sponge nevus
5. Darier’s disease
6. Hailey–Hailey disease
Group IV: No clinically evident lesion but oral cavity issusceptible to OSCC.
1. Immunosupression
a. AIDS
b. Immunosupression therapy (for malignancy or organ transplant)
2. Alcohol consumption and abuse
3. Nutritional deficiency
a. Sideropenic dysphagia
b. Deficiency of micronutrients
New classification of OPMD . Oral oncology head and neck 2011
INTRODUCTION
DEFINITION
“Insidious chronic disease affecting any part of the oral cavity and
sometimes the pharynx. Although occasionally preceded by and /or
associated with vesicle formation, it is always associated with juxta-
epithelial inflammatory reaction followed by a fibro-elastic change of the
lamina propria with epithelial atrophy leading to stiffness of mucosa and
causing trismus and inability to eat”
-Pindborg JJ & Sirsat S.M (1966)
Pindborg JJ, Sirsat SM. Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol 1966; 22 (6):
764-779.
“Slowly progressive disease characterized by the fibrous
bands in the oral mucosa, ultimately leading to severe
restriction of mouth movement including the tongue.”
- World Health Organization (1978)
DEFINITION
World Health Organization Collaborating Centre for Oral Precancerous lesions. Definition of leukoplakia and related
lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978; 46: 518–39.
“ Slowly progressive chronic fibrotic disease of the oral cavity and
oropharynx, characterized by fibro elastic change and inflammation
of mucosa, leading to a progressive inability to open the mouth,
swallow or speak.”
( Burket's 10th edition )
DEFINITION
Bhattacharyya I. Red and White Lesions of the Oral Mucosa. Greenberg MS, Glick M eds. Burket's Oral Medicine. 10th ed. Spain: BC Decker Inc; 2003. 117-118.
HISTORY
Shushrutha, the greatest practitioner
of ancient medicine stated in his book
"Shushrutha Samhita' a condition
called 'Vidari' in his classification of
diseases of mouth and throat.
Ahuja SC and Ahuja U. Betel Leaf and Betel Nut in India: History and Uses. Asian Agri-History 2011;15(1):13–35.
First described among five East African women of Indian origin under the term Atrophia idiopathica(tropica) Mucosae Oris by Schwartz 1952
Joshi in 1952 is credited to be the first person who described it and gave the present term
“Oral sub-mucous fibrosis
In the year 1954, Su. 1. P. from Taiwan described similar condition, which he called "Idiopathic Scleroderma of mouth
HISTORY
SynonymsOral Submucous fibrosis of the palate and pillars (Joshi, 1952).
Atrophia idiopathica (trophica) mucosae oris. (Schwartz)
Diffuse oral submucous fibrosis (Lal 1953).
Idiopathic scleroderma of mouth (Su, 1954).
Submucous fibrosis of palate and cheek (Desa, 1957).
Idiopathic palatal fibrosis (Rao, 1962).
Submucous fibrosis of the palate (Sirsat and Khanolkar, 1962).
Juxta epithelial fibrosis (Pindborg J.J, Sirsat, 1964)
Oral submucous fibrosis (Pindborg and Sirsat, 1966).
Subepithelial fibrosis (Goleria, 1970).
Idiopathic oral fibrosis (Krishnamoorthy, 1970).
Asian Sideropenic Dysphagia (Ramanathan K, 1981)
Basoya S. Etiopathogenesis and management of oral submucousfibrosis. Quality in Primary Care
(2015) 23 (6): 327-332
Epidemiology
Common in India, Indian subcontinents
Prevalence rate : India, Burma and South Africa : 0 to 1.2%
In India, overall incidence : 0.5%
High in southern parts of India, where the incidence of oral
cancer is also high
Africa Prevalence by gender
from 0.2-2.3% in males
and 1.2-4.57% in
females.
Age range : 20-45years
Malignant potential
rate: 7.6%
ETIOPATHOGENESIS
Local factors
Chilli
Arecanut
Misi
Systemic factors
Nutritional deficiency
Autoimmunity
Genetic susceptibility
Rajendran R.: Oral submucous fibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.
Etiopathogenesis
Capsicum annum & capsicum
frutescence
Active extract : Capsaicin
Vanillylamideof 8-methyl-6-
noneic acid
Active irritant
There are some ecological arguments against the
chilli hypothesis for example from Mexico or other
South American countries where chilli consumption
is widespread, there is no report of this condition.
The overall assessment is that there is no evidence
substantiating the etiologic role of chilli in OSMF
The suspicion that chilli is an etiological agent arose on the
basis of ecological observations and was strengthened by the
clinical and histological characteristics of this condition , i.e.
• Blood eosinophilia,
• Tissue eosinophils in the biopsy specimen
• Presence of sub epithelial vesicles
(suggested an allergic nature of this disease possibly due to
chilli intake.)
Chillies
It causes partial or complete degeneration of collagen into elastin like filaments- Sirsat
etal-1960
OSMF is the Asian version of siderophenicdysphagia where local irritant such as chillies
brings the changes-Ramanathan et al 1981
Rajendran R.: Oral submucous fibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.
Betel nut
Areca nut –unhusked
whole fruit of the areca nut
tree
Betel nut –inner karnel or seed which is obtained after removing husk
Common names:Betel nut or quid , Areca nut = EnglishThat Tha or Kun Ja = Myanmar (Burma)Supadi = NepaleseSupari = Hindi, BengaliAdike = KannadaMak or Mahk = ThaiPinlang, Pinang = China & Sarawak
India:o Paan , Paan-Gutkhao Paan masala (dry form, no tobacco)o Gutkhao Kwai (wet variety of betel-nut)
Etiopathogenesis
Botanical description:· Scientific name : Areca catechu Linnaeus· Family : Arecaceae (Palmae), palm family· Subfamily : Arecoideae
Lingappa A, Nappalli D, Sujatha GP, Shiva Prasad S. Areca nut: to chew or not to chew? e-Journal of Dentistry July - Sep 2011 Vol 1 Issue 3
The word ‘Areca’ isderived from the Malay word adakka (areca nut) or fromadakeya, the Indian equivalent
Arecanut
Alkaloids(0.2-0.7%) Flavanoids Others
Arecoline,
Arecaidine
Guvacine
Isoguvacine
Arecolidine
Guvacoline
Tannic acid,(14-
18%)
D. Catechol
Fats(3%)
Carbohydrates(47%
)
Proteins(5%)
Water (30%)
mineral matters
Stimulate cultured
fibroblasts to proliferate
and synthesize collagen.
Increase the stabilization of
collagen by enhancing the
cross linking of collagen
Composition of areca nut (Khanna JN, Andrade NN (1995)
lime
These cause local irritation and damage to the mucosa with vesicle
and ulceration on susceptible individual.
Lime in betel quid causes constant aberration of oral mucosa, allowing
direct access to the carcinogens
It is purified by soaking in lemon juice and then
prepared for use.
Lime is a calcium-containing inorganic material in which carbonates, oxides and hydroxides predominate (calcium oxide or calcium
hydroxide)Lime is obtained from lime stone
Aids in the digestion of food.Cures chronic diarrhea,
Etiopathogenesis
Tropical Pacific, Asia, and parts of east Africa.
Etiopathogenesis
The current production of arecanut in the world is about 0.613 million tonnes from an area of 0.476 million hectares.
India ranks first in both area (58%) and production (53%) of arecanut.
The current world productivity of arecanut is 1.287tonnes/ha.
China ranks first in arecanut productivity with 3.752 tonnes/ha.
India ranks fourth in terms of productivity (1.189 tonnes/ha).
Karnataka, Kerala, Assam and West Bengal are the important states growing arecanut.
Arecanut is mainly produced in Shimoga, South Kanara, North Kanara and Chickmagalore in Karnataka, Southern India
http://www.krishisewa.com/articles/production-technology/61-arecanut.html
Tobacco
Smoking form
Smokeless form
BidiChillumChuttaCigarette
DhumtiHookahHookli
KhainiManipuri TobaccoMishri/ MasheriPaanSnuffGudhakuZarda
Etiopathogenesis
Quid - A substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or
any manufactured or processed form’
N’-nitrosonornicotine is produced by bacterial and enzymatic nitrosation of nicotine and can be found by reaction of salivary nitrates with nornicotine
N’-nitrosonornicotine levels increased 44% when tobacco was mixed with saliva
N’-nitrosonornicotine extracted from chewing tobacco with saliva is approximately 1000 times that found in cigarette smoke
Etiopathogenesis
Smokeless tobacco KHAINI
Powdered sun-dried tobacco, slaked lime (CaOH2) paste mixture occasionally used with areca nut.
Placed in mouth/ chewed.
Commonly used - Maharashtra
MAINPURI TOBACCO
CONTAINS : tobacco, slaked lime, finely cut arecanut, camphor, cloves
Commonly used – Uttar Pradesh
Etiopathogenesis
PAAN
Refers to the betel leaf itself – quid
Quid contains : arecanut, lime, aniseed, cardamom, cinnamon, coconut, cloves, sugar, tobacco wrapped in betel leaf.
Etiopathogenesis
Misi is a black coloured powder containing various
chemical substances like washing soda, borax, powdered
alum, charcoal of myrobalan and fillers earth in varying
proportions which is used as cosmetic for the teeth and
gums.
Group of authors found 30 cases of OSMF in eastern
Uttar Pradesh, where villagers were constantly using
“Misi” as a cosmetic to keep their teeth clean and shiny.
In their study group
Misi
Ramachandran S, Annigeri RG, Sree Vijayabala G. Pathogenesis of Oral Submucous Fibrosis: The Past and Current Concepts. International Journal of Oral & Maxillofacial Pathology 2012;3(2):27-36.
Genetic
Predisposition
Collegen-related genes COL1A2, COL3A1,
COL6A1, COL6A3 and COL7A1 have been
identified as targets of transforming growth
factor-b (TGF- b) and induced fibroblasts at
an early stage of the disease
Basoya S. Etiopathogenesis and management of oral submucous fibrosis. Quality in Primary Care (2015) 23 (6): 327-332
Nutritional
deficiency
Repeated vesiculations and ulcerations
Vitamin B complex deficiency
Precipitated by the effect of defective nutrition due to impaired food intake in advanced cases
Impaired cellular utilization of iron explains the presence of hypochromic microcytic anemia.
Etiopathogenesis
Rajendran R.: Oral submucous fibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.
Due to resemblance to scleroderma
Female predominance
Age group
Presence of autoantibodies
Presence of circulatory immune complex (increased Ig complex)
Betal nut can act as heptans to produce antibodies to parietal cells
Autoimmunity
Rajendran R.: Oral submucous fibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.
Normal Oral MucosaIron and other nutritional
deficiencies
Tobacco, Lime and Betel nut
Genetic abnormalities
Autoimmunity
HSV/ HPV
Oral Submucous Fibrosis
Immune system changes
1) MULTIFACTORIAL - Pillai R Pathogenesis
Pillai R, Balaram P, Reddiar KS. Pathogenesis of OSMF. Relationship to risk factors associated with oral cancer. 2015; 69(8):2011-20.
A multifactorial model for the pathogenesis of OSF. Bold arrows show effects mediated by various factors through the immune system, whereas broken arrows show possible direct effects of the factors on oral mucosa.
2) Molecular Pathogenesis : Collagen Production Pathway (Rajalalitha S, Vali S. 2005)
Pathogenesis
Roberts AB, Flanders KC, Kondaiah P, Thompson NL, Van Obberghen- Schilling E, et al. Transforming growth factor
beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm
Res.1988; 44: 157-97.
Procollagenase
TGF-ß
Activation of PAI geneActivation of TIMP gene
PAI
Inhibits activated collagenases
TIMPs
Plasminogen Plasmin
Collagenase activity
Collagenase
Flavonoids in areca nut
Collagen Degradation
PAI- Inhibitor of Plasminogen Activator
Pathogenesis
Roberts AB, Flanders KC, Kondaiah P, Thompson NL, Van Obberghen- Schilling E, et al. Transforming growth factor
beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm
Res.1988; 44: 157-97.
TIMP -tissue inhibitor of matrix metalloproteinase
BMP- Bone Morphogenic ProteinPCP- Pro Collagen C ProteinaseLOX- Lysyl Oxidase
Pathogenesis
Roberts AB, Flanders KC, Kondaiah P, Thompson NL, Van Obberghen- Schilling E, et al. Transforming growth factor
beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm
Res.1988; 44: 157-97.
Overall effect of activated TGF –ß Pathway
Increase in collagen production
Decrease in collagen degradation
Increase in collagen (insoluble form)
Fibrosis
Oral Submucous Fibrosis
Pathogenesis
Roberts AB, Flanders KC, Kondaiah P, Thompson NL, Van Obberghen- Schilling E, et al. Transforming growth factor
beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm
Res.1988; 44: 157-97.
Increased collagen synthesis (by Arecaidine)
1. Fibroblast proliferation
2. Upregulated collagen genes
3. Upregulation of COX2
4. Increased profibrotic cytokines- TGF-β
5. Gene polymorphisms -TGF-β
Decreased collagen degradation
1. Resistant to degradation
2. Increased copper
3. Upregulation of Lysyl oxidase
4. Decreased obliteration (by Tannins)
5. Stabilization of collagen structure by Tannins
& Catachins
6. Stabilization of extracellular matrix
7. Inhibition of collagen phagocytosis
3) Angadi P et al. (2011)
Pathogenesis
Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.
Pathogenesis
Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.
Pathogenesis
Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.
Increase in collagen production
Decrease in collagen degradation
Increased collagen (insoluble cross-linking of insoluble form of collagen)
Fibrosis
Oral Submucous Fibrosis
Rajalalitha P, Vali S. Molecular pathogenesis of oral submucous fibrosis--a collagen metabolic disorder. J Oral Pathol Med. 2005 Jul; 34 (6): 321-8.
4) Muscle degeneration mechanism - Khanna JN, Andrade NN (1995)
Pathogenesis
Khanna JN, Andrade NN. Oral submucous fibrosis: a new concept in surgical management—report of 100 cases. Int J Oral Maxillofac Surg 1995;24(6):433-439
Kandasamy M, Anisa N, Rahman A, Rajan MA, Prakash A, Lal J. Etiopathogenesis of Oral Submucous Fibrosis - Review Of Literature. J Adv Med Dent Scie Res 2015;3(3):53-58.
5) Role Of Saliva – Salivary Coagulopathy- Chaturvedi VN et al (1991)
Normal mucosa
Slaked Lime Chronic Irritant
Chemical Burn
Microhaemorrhage
Laying down fibroblast
Coagulation
Salivary coagulation factor
Mechanical burn
Precipitate fibrosis
OSMF
Calcium
PlasmaFibrinogen
Altered immunity
Pathogenesis
Chaturvedi VN, Sharma AK, Chakrabarati S. Salivary coagulopathy and humoral response in oral submucous fibrosis. JIDA 1991;62:51- 9.
Clinical features
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
BLANCHING Clinical features
Reticular blanching
Diffuse blanching
Localized blanching
Labial mucosa
Ventral surface Dorsal surface
Gingiva
Clinical features
Bud shaped uvula
Restricted tongue movement
Hockey stick appearance of uvula
Depapilated tongue Associated with premalignancy
MILD/ EARLY PHASE MODERATE PHASE LATE PHASE
Recurrent stomatitis and
vesiculation (palate)
Burning sensation to spicy
food
Mild blanching of oral
mucosa
No restriction of mouth
opening and tongue
movements, such as
protrusion
Burning sensation even
without stimuli
Blanching moderate to severe
Mouth opening and tongue
protrusion reduced by about
33%
Tongue is less flexible
Palpable bands present
Haematological examination:
mild anemia
Burning sensation continues
Severe blanching
Mouth opening and tongue
protrusion reduced by about
66%
Tongue may appear fixed and
cheek flexibility reduced
Thick palpable bands
Hematological examination:
iron deficiency anemia
Nutritional deficiency:
angular cheilitis
Mubeen. White lesions. In: Venkataraman BK. Diagnostic Oral Medicine.1st ed. Haryana: Wolters Kluwer Health; 2013. p. 91-99.
Clinical features
Classification / Grading/ Staging
More CB, Gupta S, Joshi J, Varma SN. Classification System for Oral Submucous Fibrosis. Journal of Indian Academy
of Oral Medicine and Radiology, January-March 2012;24(1):24-29
Classification / Grading/ Staging
Stage I: Stomatitis and vesiculation
Stage II: Fibrosis
Stage III: As its sequelae
Classification based on clinical features of OSMF
JV Desa (1957)
More CB, Gupta S, Joshi J, Varma SN. Classification System for Oral Submucous Fibrosis. Journal of Indian Academy
of Oral Medicine and Radiology, January-March 2012;24(1):24-29
Tupkari JV, Bhavthankar JD, Mandale MS. Oral submucous fibrosis (OSMF). A study of 101 cases. Journal of Indian Academy of Oral Medicine and Radiology 2007;19(2): 311-18.
Classification based on clinical features of OSMF
Pindborg JJ in 1989
•Stomatitis includes erythematous mucosa, vesicles, mucosal ulcers, melanotic mucosal pigmentation and mucosal petechiae.Stage I
•Fibrosis occurs in healing vesicles and ulcers, which is the hallmark of this stage.
•Early lesions show blanching of the oral mucosa.
•Older lesions include vertical and circular palpable fibrous bands in the buccal mucosa and around the mouth opening or lips.
•This results in a mottled marble like appearance of the mucosa because of the vertical thick, fibrous bands in association with a blanched mucosa.
•Reduction of mouth opening, stiff tongue, blanched and leathery floor of the mouth, fibrotic and depigmented gingiva, rubbery soft palate with decreased mobility, blanched and atrophic tonsils, shrunken bud like uvula and sunken cheeks, not commensurate with age or nutritional status.
Stage II
Classification / Grading/ Staging
Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58
Classification based on clinical features of OSMF
Pindborg JJ in 1989
• Sequelae of OSMF are as follows:
• Leukoplakia is found in more than 25% of individuals with OSMF.
• Speech and hearing deficit may occur because of involvement of tongue and the Eustachian tube.
Stage III
Classification / Grading/ Staging
Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58
Classification based on clinical features of OSMF
SK Katharia et al (1992)
SCORE MOUTH OPENING / INTERINCISAL DISTANCE IN mm
0 41 or more
1 37-40
2 33-36
3 29-32
4 25- 28
5 21-24
6 17-20
7 13-16
8 09-12
9 05-08
10 0-04
Classification / Grading/ Staging
Katharia SK, Singh SP, Kulshreshtha VK. The effects of placenta extract in management of oral submucous fibrosis. Indian Journal of Pharmacology 1992;24;181-83.
Classification based on clinical features of OSMF
Group A: >35 mm
Group B: Between 30 and 35 mm
Group C: Between 20 and 30 mm
Group D: <20 mm
Lai DR (1995)
Classification / Grading/ Staging
Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58.
Classification based on clinical features of OSMF
R Maher et al (1996)
Involvement of one-third or less of the oral cavity (if three or less of the
above sites are involved).
Involvement of one to two-thirds of the oral cavity (if four to six intraoral
sited are involved).
Involvement of more than two-thirds of the oral cavity (if more than six
intraoral sites are involved).
Classification / Grading/ Staging
More CB, Gupta S, Joshi J, Varma SN. Classification System for Oral Submucous Fibrosis. Journal of Indian Academy
of Oral Medicine and Radiology, January-March 2012;24(1):24-29
Classification based on clinical features of OSMF
Haider et al. (2000)Clinical staging:
- Stage 1: faucial bands only
- Stage 2: faucial & buccal bands
- Stage 3: faucial, buccal & labial bands
Functional staging:
- Stage 1: mouth opening >20 mm
- Stage 2: mouth opening 11-19 mm
- Stage 3: mouth opening <10 mm
Classification / Grading/ Staging
Haider SM, Merchant AT, Fikree FF, Rahbar MH. Clinical and functional staging of oral submucous
fibrosis. Br J Oral Maxillofac Surg. 2000 Feb;38(1):12-5.
Classification based on clinical features of OSMF
Group I: Only symptoms, with no
demonstrable restriction of mouth
opening.
Group II: Limited mouth opening 20
mm and above.
Group III: Mouth opening less than
20 mm.
Group IV: OSMF advanced with limited mouth
opening. Precancerous or
cancerous changes seen throughout the
mucosa.
Ranganathan K et al (2001)
Classification / Grading/ Staging
Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58.
Classification based on clinical features of OSMF
Rajendran R (2003)
EARLY OSF: Burning sensation in the mouth. Blisters especially on the palate, ulceration or recurrent generalized
inflammation of oral mucosa, excessive salivation, defective gustatory sensation and dryness of mouth.
ADVANCED OSF: Blanched and slightly opaque mucosa, fibrous bands in buccal mucosa running in vertical direction.
Palate and faucial pillars are the areas first involved. Gradual impairment of tongue movement and difficulty in mouth
opening.
Classification / Grading/ Staging
George Antony, Sreenivasan BS, S Sunil, et al. Potentially malignant disorders of oral cavity. Journal of Oral and Maxillofacial Pathology 2011;2(1):95-100.
Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58.
Classification based on clinical features of OSMF
Nagesh and Bailoor (1993)
Stage I early OSMF: Mild blanching, no restriction in mouth Burning sensation on taking spicy food or hot beverages.
Stage II moderate OSMF: Moderate to severe blanching, mouth opening reduced by 33%, cheek flexibility reduced, burning sensation also in absence of stimuli, palpable bands felt. Lymphadenopathy either unilateral or bilateral and demonstrable anemia on hematological examination.
Stage III severe OSMF: Burning sensation is very severe patient unable to do dayto- day work, more than 66% reduction in the mouth opening, cheek flexibility and tongue protrusion. Tongue may appear fixed. Ulcerative lesions may appear on the cheek, thick palpable bands and lymphadenopathy bilaterally evident.
Classification / Grading/ Staging
Bailoor D, Nagesh KS. Fundamentals of oral medicine and radiology (1st ed),2005.
Classification based on clinical features of OSMF
Group A—mild cases: Only occasional symptoms, pallor, vesicle formation, presence of one or two solitary palpable bands, loss of elasticity of mucosa, variable tongue involvement with protrusion beyond vermillion border. Mouth opening >3 cm.
Group B—moderate cases: Symptoms of soreness of mucosa or increased sensitivity to chilies, diffuse involvement of the mucosa, blanched appearance, buccal mucosa tough and inelastic fibrous bands palpable, considerable restriction of mouth opening (1.5 to 3 cm) and variable tongue movement.
Group C—severe cases: Symptoms more severe, broad fibrous bands palpable, blanched opaque mucosa, rigidity of mucosa, very little opening of mouth (less than 1.5 cm), depapillated tongue and protrusion of tongue very much restricted.
Tinky Bose and Anita Balan (2007)
Classification / Grading/ Staging
Bose Tinky, Balan Anita. Oral submucous fibrosis-A changing scenario. Journal of Indian Academy of Oral Medicine and Radiology 2007;19(2):334-40.
Classification based on clinical features of OSMF
Stage I: Mouth opening >45 mm
Stage II: Restricted mouth opening 20 to 44 mm
Stage III: Mouth opening <20 mm
Kiran Kumar et al (2007)
Classification / Grading/ Staging
Kumar Kiran, Saraswathi TR, Rangnathan K, Devi Uma M, Elizabeth Joshua. Oral submucous fibrosis: A clinicohistopathological study in Chennai. Indian Journal of Dental Research 2007;18(3):106-11.
Classification based on clinical features of OSMF
Chandramani More et al (2011)
Stage 1 (S1)
•Stomatitis and/or blanching of oral mucosa.
Stage 2 (S2)
•Presence of palpable fibrous bands in buccal mucosa and/or oropharynx, with /without stomatitis.
Stage 3 (S3)
•Presence of palpable fibrous bands in buccal mucosa and/or oropharynx, and in any other parts of oral cavity, with/ without stomatitis.
Stage 4 (S4)
•a. Any one of the above stage along with other potentially malignant disorders, e.g. oral leukoplakia, oral erythroplakia, etc.
•b. Any one of the above stage along with oral carcinoma.
Clinical staging
Classification / Grading/ Staging
Reddy V, Wanjari PV, Reddy N, Reddy P. Oral Submucous Fibrosis: Correlation of Clinical Grading to various habit
factors. International Journal Of Dental Clinics 2011:3(1): 21-24.
Classification based on clinical features of OSMF
Chandramani More et al (2011)
M1
• Interincisalmouth opening up to or greater than 35 mm.
M2
• Interincisalmouth opening between 25 and 35 mm
M3
• Interincisalmouth opening between 15 and 25 mm
M4
• Interincisalmouth opening less than 15 mm.
Functional staging
Classification / Grading/ Staging
Reddy V, Wanjari PV, Reddy N, Reddy P. Oral Submucous Fibrosis: Correlation of Clinical Grading to
various habit factors. International Journal Of Dental Clinics 2011:3(1): 21-24.
Prakash R. et al
Based on morphologic variants of soft palate
Type 1: Leaf shaped
Type 2: Rat tail shaped
Type 3: Butt shaped
Type 4: Straight line
Type 5: Deformed S
Type 6: Crook shaped
Classification / Grading/ Staging
Classification based on Histopathological features of OSMF
Pindborg JJ and Sirsat SM (1966)
VERY EARLY STAGE:
Finely fibrillar collagen dispersed with marked edema. Plump young fibroblast containing abundant cytoplasm.
Blood vessels are dilated and congested.
Inflammatory cells, mainly polymorphonuclearleukocytes with occasional eosinophils are found.
EARLY STAGE:Juxta-epithelial area shows early hyalinization. Collagen still in separate thick bundles.
Moderate number of plump young fibroblasts is present.
Dilated and congested blood vessels.
Inflammatory cells are primarily lymphocytes, eosinophils and occasional plasma cells.
MODERATELY ADVANCED STAGE:
Collagen is moderately hyalinized.
Thickened collagen bundles are separated by slight residual edema.
Fibroblastic response is less marked.
Blood vessels are either normal or compressed.
Inflammatory exudate consists of lymphocytes and plasma cells.
ADVANCED STAGE:
Collagen is completely hyalinized.
Smooth sheets with no separate bundles of collagen is seen.
Edema is absent.
Hyalinized area is devoid of fibroblasts.
Blood vessels are completely obliterated or narrowed.
Inflammatory cells are lymphocytes and plasma cells.
Classification / Grading/ Staging
Rangnathan K, Gauri Mishra. An overview of classification schemes for oral submucous fibrosis. Journal of Oral and Maxillofacial Pathology, 2006 Jul-Dec;10(2):55-58.
Classification based on Histopathological features of OSMF
Kiran Kumar et al (2007)
1. Grade I: Loose, thick and thin fibers
2. Grade II: Loose or thick fibers with partial
hyalinization
3. Grade III: Complete hyalinization
Classification / Grading/ Staging
Kumar Kiran, Saraswathi TR, Rangnathan K, Devi Uma M, Elizabeth Joshua. Oral submucous fibrosis: A clinicohistopathological study in Chennai. Indian Journal of Dental Research 2007;18(3):106-11.
Histopathological features
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.
ANEMIC STOMATITIS: because of presence of
Dysphagia concomitant with OSMF, patient will
have reduced diet and hence nutritional deficiency and finally resulting anemia
SCLERODERMA: a connective tissue disorder resulting in trismus and
stiffness of mucosa
RADIATION FIBROSIS: if the patient gives history of
radiation therapy
VERTICAL SCAR BAND: if patient gives history of minor or major surgical
procedures
Differential
Diagnosis
Diagnosis
HISTORY OF BETEL QUID CHEWING
INTERNATIONAL CONSENSUS
CRITERIA
LABORATORY INVESTIGATIONS
Palpable fibrous bandsMucosal texture feels
tough & leatheryBlanching of mucosa
together
Decreased Hb, iron, protein and vitamin B complex levels
Increased erythrocyte sedimentation rate
Assessment of tongue protrusion
Kumar SM, Shanmugam S. Ramalakshmi M, Jayashankar S. Various treatment modalities and visceral organ involvement (cardiac) in oral submucous fibrosis. A clinical study. JIAOMR 2011;23(3) 190-194
Diagnosis
Subject will be asked to protrude the tongue, as much as possible at maximal mouth
opening.
Distance between mesio-incisal angle of upper / lower left incisors and tip of tongue will
be measured.
If incisors are absent, crest of lower alveolar ridge will be taken as the point of reference.
Three measurements will be taken and the average value will be calculated and recorded.
Two points measured between at 1/3 rd the distance from the angle of mouth on a line joining the tragus of ear & angle of mouth
Subject is then asked to blow his cheek fully & the distance measured between the 2 points marked on the cheek
Males 1.3 cm
Females 1.08 cm
Assessment of cheek flexibility
Diagnosis
CF = V1 – V2
DiagnosisAssessment of mouth opening
MEAN INTERINCISAL
DISTANCE
Male: 51.3 mm (Range 39–65 mm)
Female: 44.3 mm (Range 36–56 mm)
{Indian males is 51.3±8.3 mm,
females is 44.3±6.7 mm}
Mezitis M, Rallis G, Zachariades N. The normal range of mouth opening. J Oral Maxillofac Surg.2015;47:1028.
INVESTIGATIONS
Hematological & Biochemical
Serological
Cytogenetics
Histopathological
Immunohistochemical
Immunofluorescence
Tissue Culture
INVESTIGATIONS
VitaminB 12, folate and iron
Anaemia
Eosinophilia
serum iron
Decrease in Increase in total iron-binding capacity
blood sedimentation rate
Gammaglobulin
serum Mucoproteins, Mucopolysaccharides
Anti-streptolysin titre 0 (measured in Todd's units
LDL, VLDL
• Albumin• Lactate dehydrogenase
iso-enzyme ratio (LDH IV/LDH II)
• Serum copper and zinc ratio
• Lipid profile • HDL , total cholesterol
Hematological & Biochemical
2) Serological 1. ↑ High-affinity rosette forming cells (HARFC)
2. ↑ Serum levels of IgA, IgD and IgE (Rajendran R
et al- 1986)
3. HLA typing(A10, B7, DR3) (Caniff et al 1981)
4. ↑ β2 microglobulin (Anil S et al 1995)
3) Cytogenetics 1. Sister chromatid exchange (SCE)
2. AgNOR. Silver-binding nucleolar organizer
region proteins (AgNORs)
3. Transforming growth factor- β-1 ( infrequent but
exist in selected loci in OSMF)
INVESTIGATIONS
4) Immunohistochemistry 1. ↑ Cytokeratin (CK-2)-
2. ↓CK-17- lalii A et al
3. ↑ Cystatin C - Tsai CH et al -2007
4. ↑ Basic fibroblast growth factor- in early stages -Bishen KA et al
5. ↑ Heat shock protein 47 (by RT-PCR) - Yang SF et al – 2008
6. ↑ TIMP1, 2, PAI – 1 - Shung-FA et al
7. ↑ p53- Chiang CP
8. ↑ Retinoic acid receptor beta (RARbeta)- Kaur J et al -2004
5) Immnofluorescence 1. Hyalinized stroma can be distinguished from the
Amyloid infiltration of Amyloidosis
2. Using :
3. Congo red staining and
4. Thioflavin-T staining
INVESTIGATIONS
Antioxidants : b-carotene, vitamins A, C and E, zinc
Lycopene
Curcumins
Oxitared capsule
Nutrients, Micronutrients and Anti-
oxidants
Biogenic stimulation
Placental extract
Proteolytic enzymes
• Collagenase
• Hyaluronidase
IM
MU
NE
MO
DU
LA
TIO
NTopical
Betamethasone
Triamcinolone acetonide
Intralesional
Chymotrypsin
Interferon gamma (IFN-γ)
Hydrocortisone
Betamethasone
Methylprednisolone
Triamcinolone diacetate
Dexamethasone
Systemic
Levamisole
Immune milk
Colchine
1. Pentoxifylline
2. Nylidrin hydrochloride
Promotion of blood flow
b-carotene, vitamins A, C and E, zinc
Lycopene
Curcumins
Oxitared capsule
Nutrients, Micronutrients and Anti-oxidants
Antioxidants are protective agents that inactivate reactive oxygen species and therefore significantly delay or prevent oxidative damage
Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent.
Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions.
ANTIOXIDANTS
Antioxidants such as superoxide dismutase, catalase and glutathione peroxidase are naturally present within human cells
In addition, antioxidants such as vitamin E, vitamin C, polyphenols and carotenoids are available from food.
Rui L et al Lycopene: features and potential significance in the oral cancer and precancerous lesions J Oral Pathol Med 2011;40: 361–368
Kelkel M et al. Antioxidant & antiproliferative propertiesv of lycopene. Free radical research, 2011;45(8):925-940.
The antioxidant potential has been ranked as followslycopene > α-tocopherol > α-carotene > ß-cryptoxanthin > zeaxanthin= ß-carotene > lutein
ANTIOXIDANTS
Beta carotene
Hydrophobic molecules with little
or no solubility in water
Dark green, orange or yellowish vegetables,
such as spinach, carrots, sweet potato, mango, papaya, and
oranges
Vitamin A precursor
Antioxidizing action-ligation between
beta-carotene and oxygen, which is an
unstable reactive molecule, thus
diminishing the damaging effects of
free radicals
ANTIOXIDANTS
Maintains epithelial integrity
Plays an important role in induction and control of epithelial differentiation in mucous secretory and keratinization tissue,
Basal cells are stimulated to produce mucous secreting cells.
The progress of premalignant cells to malignancy is delayed or arrested.
It improves the mucosal colour, reduction of fibrous bands and improvement in mouth opening.
Vitamin A
Usage: Vitamin A 50,000 IU orally daily (12Weeks)
ANTIOXIDANTS
Zinc
Epithelializing agent
Dosage : Zinc sulphate 220mg TDS
Zinc alone /in combination with vitamin-A better in grade I & II
Zinc + cortisone effective in grade III
Increases the extent of relief and no relapse was observed upto a period
of 15 months
• Acts as antioxidant prevent formation of toxic substances and enhance the indigenous concentration of Vitamin A.
• Vitamin E by enhancing the concentration of Vitamin A helps in improvement of mucosal color, burning sensation ,and mouth opening.
Vitamin E
ANTIOXIDANTS
Vitamin B complex with iodine (injection
ranodine)
1. I.M -2ml daily
2. Contains
Methyl tri oxyethyl iodomine
Vitamin B1- 1mg
Vitamin B6-0.3 mg
Vitamin B2- 0.6mg
Nicotinamide- 15 mg
Calcium pantothenate- 1mg
Vitamin B-complex tablets
1. Orally in a dose of 200 mg twice a day
ANTIOXIDANTS
Beta carotene- 10mg
Zinc sulphate monohydrate-27.45mg
Monohydrated selenium dioxide- 70mcg
Manganese sulphate- 2mg
Copper sulphate- 1mg
ANTIOXIDANTS COMBINATIONS
Antoxid (Capsule)
ANTIOXIDANTS
Alpha - lipoic acid is a sulfur-containing substance that is readily converted to and from its reduced form, dihydrolipoic acid.
Alpha - lipoic acid acts as a coenzyme in reactions that occur in the Krebs cycle; specifically it is involved in the decarboxylation of pyruvate and some other alpha-keto acids.
It may well be the perfect antioxidant. Alpha - lipoic acid has researched for use in the treatment of HIV and diabetes
Because it dissolves in both water and fat, this so-called "universal antioxidant" is able to scavenge more wayward free-radical cells than most antioxidants, the majority of which tend to dissolve in either fat or water but not both.
α-Lipoic AcidANTIOXIDANTS
b-carotene, vitamins A, C and E, zinc
Lycopene
Curcumins
Oxitared capsule
Nutrients, Micronutrients and Anti-oxidants
Antioxidants
Lycopene ANTIOXIDANTS
Lycopene is a bright red carotenoid pigment.
Its name is derived from the tomato's species classification Solanum lycopersicum
Tomatoes, watermelons, guava,graves,
red chilli
Tomato & tomato-based food – 85%
Lycopene - carotenoid, acyclic isomer of β-carotene,highlyunsaturated hydrocarbon containing 11 conjugated and two unconjugated double bonds
induced by light, thermal energy, and chemical reactions, it can also form cis–trans isomers including 15-, 13-, 11-, 9-, 7-, 5-cis isomers .
The lycopene isomers found in human blood plasma, breast milk, and tissues are presented as isomeric mixture, with 50% as cis isomer type
Structure & properties of lycopene AO activity
Inhibition of cancer cell proliferation
Interference with growth factor stimulation
Regulation of transcription and
Restoration of gap junctions.
B
E
N
E
F
I
T
S
O
N
H
U
M
A
N
H
E
A
L
T
H
Rao A.V., Ray M.R, Rao L.G. Lycopene .Advances in food and nutrition research. 2006 3(51):100-164
Agarwal A,Roa A .Tomato lycopene and its role in human health & chronic diseases . CMAJ.2009;163(6)
Lycopene
Formulations
1. LYCOSTAR
2. LYCORED
3. LYNET
4. LYCORICH
5. LYCO-FIRST
6. LYCOAGE
7. LYCOBEL
8. LYCOBIG
9. LLYCOGOLD
10. LYCOLIFE
11. LYCOR
16 mg of lycopene daily in 2 equally divided doses
Kumar A et al, 2007
2000µg of lycopene twice daily for 3 month.
Gowda B et al 2011
DOSES
Selenium 75mcg
Lycopene 5000 mcg
Caratenoids10.33 mcg
Zinc 27.33mcg
Calcium ascorbate 50
mcg
Wheat germ oil 25mcg
Beta carotene:30mg
Selenium dioxide:200mcg
Zinc sulphate:27.5mg
Manganese:2mg
Copper:1mg
Alpha lipoic acid 50 MG
Beta-carotene 10 MG
Elemental copper 1 MG
Elemental selenium 75
MCGLycopene 5 MGVitamin E 10 IU
Zinc sulphate 27.45 MG
Lycopene 15 mg Zinc 5 mg
Vitamin C 40 mg Vitamin D
20 mcg
b-carotene, vitamins A, C and E, zinc, copper, manganese and selenium
Lycopene
Curcumins
Spirulina
Oxitared capsule
Nutrients, Micronutrients and Anti-oxidants
ANTIOXIDANTS
ANTIOXIDANTS
Das D, Balan A, Sreelatha KT. Comparative Study of the Efficacy of Curcumin and Turmeric Oil as Chemopreventive Agents in Oral Submucous Fibrosis: A Clinical and Histopathological Evaluation. Journal of Indian Academy of Oral Medicine and
Radiology, April-June 2012;22(2):88-92.
Curcumin is active ingrediant of turmeric.
Curcumin
ACTIONS
Anti-inflammatory
Antioxident
Fibrinolytic
Inhibition of lipid peroxidation
Checking cellular proliferation/
promotes apoptosis
Inhibition of collagen synthesis
DOSE
500mg
twice
daily
Das D et al-2011Significant improvement was observed in the clinical sign, symptoms and even
histopathologically.
Antioxidants (b-carotene, vitamins A, C and E, zinc, copper, manganese and selenium)
Lycopene
Curcumins
Oxitared capsule
Nutrients, Micronutrients and Anti-oxidants
Contents
Amra (Mangifera Indica)
Ashwagandha (Withania Somnifera)
Garjara (Daucus Carota)
Yashtimadhu (Glycyrrhiza Glabra)
Draksha (Vitis Vinifera)
Amalaki (Emblica officinalis)
Lavanga (Syzygium Aromaticum )
ANTIOXIDANTS
Oxitard
Doses2 capsules twice daily for
period of 3 month
Placental extract
Placentrex was first introduced By Flator(1933) and later developedin 1953. It owes its inception to corneal transplant.
ACTIONS OF PLACENTREX
• Accelerates cellular metabolism.
• Aids in absorption of exudates.
• Stimulates regenerative process.
• Increase physiological function of
organs.
• Produces significant
enhancement of wound healing.
• Has anti-inflammatory effect
FLATOR THEORY
“Animal and vegetable tissues whensevered from the parent body and exposedto a condition unfavorable, undergobiological re-adjustments leading to thedevelopment of substances in state oftheir survival to ensure their vitality asBIOGENIC STIMULATORs.Such tissues or their extracts whenimplanted or injected into the body afterresistance to pathogenic factorsstimulates metabolic or regenerativeprocess thereby favoring recovery.”
It is an aqueous extract of human placenta that contains nucleotides, enzymes, vitamins, aminoacids & steroids.
Thakur.G et al.Does Topical Application of Placental Extract Gel on Postoperative Fibrotomy Wound Improve Mouth
Opening and Wound Healing in Patients With Oral Submucous Fibrosis? J.oral max.surg.july.2015. 1439.e1–
1439.e10
1. Nucleotides –RNA , DNA, ATP
2. Enzymes –
a. Alkaline & acid phosphatase,
b. Glutammic Oxalo-acetic acid
c. Transaminase
d. Glutamic acid
e. Pyruvic acid transaminase
3. Vitamin – Vit E, B1, B6, B12, Pantothenic acid , nicotinic acid, biotin, PABA, Folic acid
4. Steroids – 17 ketosteroids
5. Cholesterol ,
6. Amino acids,
7. Fatty acids &
8. Trace elements. Zn,Sn, Mg
Placental extracts contains
Placental extract
Available in 4 formsAqueous solution of human placentaLipoid extractsImmuno-gamma globulinsTissue coagulants
Thakur.G et al.Does Topical Application of Placental Extract Gel on Postoperative Fibrotomy Wound Improve Mouth Opening and Wound Healing in Patients With Oral Submucous Fibrosis? J.oral
max.surg.july.2015. 1439.e1–1439.e10
DOSE
• 2 ml of solution deposited at interval of 3 days for in divided region.
• This course can be repeated after a month if required.
(Kakar et al, 1985),
(Gupta and Sharma, 1988),
(Katharia et al,1992),
(Rananjaneyulu and Rao, 1980),
(Gupta et al, 1992)
• 4mg dexamethasone bi weekly
• 1500 IU of hyaluronidase with 1cc of lignocaine bi weekly
• 4mg of dexamethasone and 1500 IU of hyaluronidase
• 2cc Placentrex biweekly
Karkarpuri et al (1985)
• injection of hyaluronidase 1.5 cc for one group and 2cc Placentrex once a week for the other group for 12 consequent weeks, they reported failure rate of 7.2% for hyaluronidase and 31.3% for Placentrex and concluded that hyaluronidase is superior.
Sinha and Jain(1978)
• 2cc of Placentrex intralesionally a week for 10weekswas superior to cortisone
Ramananeyulu and Prabhakar Rao (1980)
Concluded that number 3 combination for seven weeks could give maximum improvement if it is followed by three weeks of hyaluronidase.
Placental extract
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).
HYALURONIDASE
(HYALASE)
Mechanism
Fibrinolytic enzyme
It helps in breakdown hyaluronic
acid
Lower viscosity of
the intercellular
cement substance
Decreases collagen
formation
DOSE
Intralesionalinjection of Hyalaseused in the dose of 1500 IU
Singh et al.Efficacy of hydrocortisone acetate/hyaluronidase vs triamcinolone acetonide/hyaluronidase in the treatment of oral submucous fibrosis Indian J Med Res
131, May 2010, pp 665-669.
It is recommended that triamcinolone acetonide (10 mg/ml) combined with 1500 IU of hyaluronidase should be given intralesionally particularly in retromolar trigone area half dose each side at 15 days interval for a total of 11 injections in 22 wk.
IMMUNE MODULATION
Topical
Betamethasone
Triamcinolone acetonide
Intralesional
Chymotrypsin
Interferon gamma (IFN-γ)
Hydrocortisone
Betamethasone
Methylprednisolone
Triamcinolone diacetate
Dexamethasone
Systemic
Levamisole
Immune milk
Colchine
Immuno-modulatory drugs
Corticosteroids
Topical•Triamcinalone acetonide 0.1% (Kenacort)
•Betamethasone – 0.5% (Betnesol)
Intralesional•Dexamethasone –4mg/ml (inj Dexona)
•Triamcinolone -40 mg/ml (inj Kenacort)
•Hydrocortisone – 25 mg/ml (inj Wycort)
MECHANISM
• Opposes the action of soluble factors released by
sensitized lymphocytes following activation by specific
antigens.
• Prevent or suppress inflammatory reactions, thereby
preventing fibrosis by decreasing fibroblastic
proliferation and deposition of collagen.
• The initial symptomatic relief could be due to the anti
inflammatory action of the steroids, which helps in
clearing the juxtaepithelial inflammationThough rare, long term intra lesionalinjection of steroid has side effects Osteoporosis, myopathies, peptic ulcer or central serous chorioretinopathy.
Glucocorticoids
Short acting drugs - hydrocortisone,
Intermediate acting drugs - Triamcinolone
Long acting drugs - betamethasone and dexamenthasone.
IMMUNE MODULATION
Chymotrypsin, an endopeptidase, hydrolyzes ester and peptide bonds,
thus acting as a proteolytic and anti-inflammatory agent.
Successful treatment of oral submucous fibrosis with local injections of
chymotrypsin, hyaluronidase, and dexamethasone is reported.
CHYMOTRYPSINIMMUNE MODULATION
Kerr AR et al. A systematic review of medical interventions for oral submucous fibrosis and future research opportunities. Oral Diseases (2011) 17 (Suppl. 1), 42–57.
INTERFERON GAMMA
Downregulates fibroblast proliferation and collagen synthesis
Upregulates the anti-fibrotic cytokines and collagenase synthesis in
the basal layer of epithelium and lamina propria.
Doses-• Intralesional injection of interferon gamma (0.01– 10.0 U/mL) 3 times a day for 6
months(Auluck et al, 2008)
•15 injections of 5o µg (0.25ml) twicw a week ver 8 week(Haque Mf et al 2001)
IMMUNE MODULATION
Haque et al.Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis. J Oral Pathol Med. 2001;30(1):12-21.
LEVAMISOLE
Anthelminthic and Immunomodulator
50 mg three times daily for three alternate weeks
Levamisole can bring about clinical improvement and is better than
antoxid and the combination regimen.
Jirge V, et al 2008
IMMUNE MODULATION
Jirge V, Shashikanth MC, Ali IM, Nisheeth A. Levamisole and antioxidants in the management of oral submucous fibrosis: A comparative study. J Indian Acad Oral Med
Radiol. 2008;20:135–40.
Balaji rao et al. levamisole 150 mg-once daily for 3 days in a week for 6-8 weeks
Immune milk is a kind of skimmed
milk produced from cows immunised
with multiple human intestinal
bacteria.
It has good anti-inflammatory effect
& contains moderate amounts of Vit. A, C, B1, B2, B6, B12, nicotinic acid, pantothenic
acid, folic acid, iron, copper & zinc.
Though chemically its identical to
commercial milk but it contains 20-
30% higher concentration of
IgG type 1 antibody.
45 g of immune milk powder twice daily
for 3 months
(Tai YS, et al 2001)
Immune milk
Tai YS.et al Oral administration of milk from cows immunized with human intestinal bacteria leads to significant improvements of symptoms and signs in patients with oral submucous fibrosis. J Oral Pathol
Med.2001 Nov;30(10):618-25.
1. Pentoxifylline
2. Nylidrin hydrochloride
Promotion of blood flow
Actions • Improves microcirculation • Decreases platelet aggregation as well as granulocyte adhesion. • Inhibits neutrophil adhesion and activation. • Antithrombin, Antiplasmin activities • Fibrinolytic activity (main action for OSMF)• Decrease production of tumor necrosis factor alpha • Reduce some of the systemic toxicities mediated by interleukin-2• Increase the production of PGE2 and PGI2 by
vascular epithelium, maintains cellular integrity
DOSESPentoxifylline : 400 mg 3 times a day
for 7 months
Nylidrinhydrochloride 6mg
Trade name: ARLIDINE
Side effect-• GIT- Nausea, vomiting,• CNS-Dizziness, Headache
Sharma JK et al. 1987
Rajendran R, Rani V, Shaikh S. Pentoxifylline therapy : A new adjunct in the treatment of oral submucous fibrosis. Indian J Dent Res [ 2013];17:190-8.
Betel quid chewing habit
Chronic inflammatory process
TGF-
Collagen production
1. Anti-inflammatory / immuno-modulatory drugs
2. Anti-TGF-
Collagen degradation
PNP PCP
LOX
3. Copper chelators TIMP
Plasminogen activator system
4. Anti-LOX drugs
5. Collagenase activators
Collagenase
The most commonly used combination:
Chymotrypsin (5000 IU),
Hyaluronidase (1500 IU)
dexamethasone (4 mg)
Physiotherapy
Vitamins 50000-100000 IU
Twice weekly submucosal injections for 10 weeks to get satisfactory results
Steroid, vitamins, minerals and enzymes
Hyaluronidase and steroids
Chymotrypsin and steroids
Enzymes, chymotrypsin and steroids
Placental extracts and steroids
Steroids, peripheral vasodilator, vitamins and enzymes
Levamisole and vitamin A
Steroids and antihistaminics
COMBINATIONS
COMBINATIONS
OSMF with trismus be treated by 1.5 ml (37.5 mg) hydrocortisone acetate mixed with 1500IU of hyaluronidase injection given intralesionally half dose on each side at weekly intervalfor 22 wk
Kinger A et al 2004
Triamcinolone acetonide (10 mg/ml) combined with hyaluronidase (1500 IU) intralesionallyonce in 15 days for a total of 11 injections.
Singh M et al2010
Combination of Dexamethasone, Hyaluronidase and Placental extract gives better resultsthan with a single drug.Dose
2 ml of solution deposited at interval of 3 days for in divided region.This course can be repeated after a month if required.
Muscle stretching exercises for the mouth includes forceful mouth opening with the
help of sticks, ballooning of mouth, hot water gargling.
Forceful mouth opening have been tried with mouth gag & acrylic surgical screw.
Physiotherapy can improve oral opening but not affective to reduce pain –
Cox et al 2009
Muscle stretching exercises Physical therapy
Vijayavel. T, Ponni V. management for oral submucous fibrosis – A comprehensive review. Indian Journal of Multidisciplinary Dentistry. 2014; 4(1): 869-874.
A man diagnosed with OSMF (mouth opening at interincisallevel: 34 mm), was treated with the MED ,followed every month for next 6 months, after which the patient’s mouth opening was improved to 41 mm.
Patil PG , Patil SP. Novel Mouth-Exercising Device for Oral Submucous Fibrosis. Journal of Prosthodontics 21 (2012) 556–560.
Physical therapyMuscle stretching exercises
Diathermy
Low current of 2450 cycles x 20 watts is given.
The mechanism involved is Physiofibrinolysis.
Effective, if it is combined with other treatment modalities.
Advised in early mild and moderate advanced stages of OSMF
selective heating of juxta epithelial connective tissue is possible, thereby limiting the area treated
Physical therapy
Gupta et al 1980
Gupta D, Sharma SC. Oral submucous fibrosis- A new treatment regimen. Oral Maxillofac Surg. 1988; 46: 830-833.
The ErCr:YSGG (waterlase C-100) laser was used to release the fibrotic bands of OSMF that were causing limited
mouth opening.
It works on "hydro-photonic process" in which the laser
energy from the ErCr:YSGG is able to interact with water droplets at tissue to create water molecule excitation. This, in turn, causes water
droplet micro-expansion and propulsion that gives clean and
precise hard-tissue cut.
Analgesics,anti-inflammatory and muscle –relaxing effect.
Lasers
Vijayavel. T, Ponni V. management for oral submucous fibrosis – A comprehensive review. Indian Journal of Multidisciplinary Dentistry. 2014; 4(1): 869-874.
Physical therapy
Ultrasound treatment accelerate healing, increase the extensibility of collagen fibers, provide pain relief and selectively raises the temperature in some well circumscribed areas.
Ultrasound of dose ranging from 0.6 to 2.0 W/Cm2 pulsed 1:1 or 1:2 ( 50% or 33.3 % duty cycle), Frequency of 3 MHz, 5cm diameter transducer head for 3 to 4 minutes to each side over the cheek for 15 consecutive days with permissible one day off each week.
Vijayakumar M, Priya D. Physiotherapy for improving mouth opening & tongue protrution in patients with Oral Submucous Fibrosis (OSMF) – Case Series. International Journal of Pharmaceutical Science and
Health Care. 2013;2(3): 50-58.
Ultrasound used for therapeutic purpose has a frequency of about 0.8-1 MHz and an intensity of 0.5-3 w/cm2.
• During ultrasound therapy, cell
membrane permeability is increased
by altering sodium and potassium
ion gradients. This increased
permeability improves gas exchange
and promotes healing.
• It increases vasodilatation.
• accelerates lymph flow
• decreases inflammation and
stimulates metabolism
Ultrasound therapyPhysical therapy
Motawetz G.1987.-Excision of fibrotic
bands with sub-mucosal placements of human skin grafts.
Gupta and sharma et al 1988. Excision of fibrotic bands with
sub-mucosal placements of human
placental grafts.
Khanna and Andrade 1996-in advanced
cases bilateral temporal
myotomy,bilateralcoronoidectomy and palatal island flap.
Surgical treatment
Khanna JN, Andrade NN. Oral submucous fibrosis: a new concept in surgical management—report of 100 cases. Int J Oral
Maxillofac Surg 1995;24(6):433-439.
Surgical striping of fibrous bands
Partial thickness skin or mucosal grafts
Buccal pad of fat interposition
Myotomy
Bilateral temporalis
Temporalis
Nasolabial flap
Palatal island flaps
Lasers- diode and KTP-532 laser
Khanna JN, Andrade NN. Oral submucous
fibrosis: a new concept in surgical management—
report of 100 cases. Int J Oral Maxillofac Surg
1995;24(6):433-439.
Surgical treatment
Malignant Potential
Paymester –first person to see malignant changes in OSMF
Pindborg JJ et al (1984) : 4.5%
Murti PR et al (1985) : 4.5% to 7.6%
Cox SC, Walker DM (1996) : noted a prevalence of squamous cell carcinoma in 1/3rd of his patients.
Dayal 2000- 13.33 %SCC in OSMF group with trauma
Pindborg JJ (1972) summarized a criteria to support the precancerous nature of this disease as :
Higher prevalence of leukoplakia among submucous fibrosis patients.
High frequency of epithelial dysplasia.
Concurrent findings of submucous fibrosis in oral cancer patients.
Histological diagnosis of oral cancer without clinical suspicion, among submucous fibrosis cases.
Higher incidence of oral cancer among patients with submucous fibrosis.
Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S. Oral submucous fibrosis: Review on etiology and pathogenesis. Oral Oncol.2006;42:561-8
Hyperkeratosis
intercellular edema in the prickle
cell layers and the basal cells
Hyperplasia
Excessive fibrosis Ischaemia
Carcinoma
vulnerability of action of
Carcinogens
irritation by Exogenous
factors
Atrophy of epithelium
Malignant Potential
Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S. Oral submucous fibrosis: Review on etiology and pathogenesis. Oral Oncol.2006;42:561-8
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
Koneru A, Hunasgi S, Hallikeri K, Surekha R, Nellithady GS, Vanishree M. A systematic review of various treatment modalities for oral submucous fibrosis. J Adv Clin Res Insights 2014;2:64-72.
Conclusion
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