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Oral
Submucous
Fibrosis
Dr Sanjana Ravindra
Post Graduate
RajaRajeswari dental College,
Bangalore.
CONTENTS
 Introduction
 History
 Definition
 Epidemiology
 Nomenclature
 Etiopathogenesis
 Clinical features
 Clas...
INTRODUCTION
The oral cavity is lined with an
uninterrupted mucosa which is
continuous with the skin near
vermillion border of the lips...
OMM- Unique area of the body, which is
continuously exposed to various kinds of stresses
such as heat, cold, microorganism...
POTENTIALLY MALIGNANT DISORDERS
INTRODUCTION
PRECANCEROUS LESION
A morphologically altered tissue in which
oral cancer is ...
ORAL POTENTIALLY MALIGNANT DISORDERS
INTRODUCTION
“It is a group of disorders of varying etiologies, usually tobacco;
char...
1. HABIT RELATED
a. Tobacco associated lesions
b. Leukoplakia
c. Tobacco pouch keratosis
d. Stomatitis palatine nicotini
e...
Group III: Inherited disorders that do not
necessarily alter the clinical appearance of
local tissue but are associated wi...
DEFINITION
DEFINITION
“Insidious chronic disease affecting any part of the oral cavity and
sometimes the pharynx. Although occasional...
“Slowly progressive disease characterized by the fibrous
bands in the oral mucosa, ultimately leading to severe
restrictio...
“ Slowly progressive chronic fibrotic disease of the oral cavity and
oropharynx, characterized by fibro elastic change and...
HISTORY
HISTORY
Shushrutha, the greatest practitioner
of ancient medicine stated in his book
"Shushrutha Samhita' a condition
call...
First described among five
East African women of Indian
origin under the term
Atrophia idiopathica
(tropica) Mucosae Oris ...
SYNONYMS
SynonymsOral Submucous fibrosis of the palate and pillars
(Joshi, 1952).
Atrophia idiopathica (trophica) mucosae oris.
(Sc...
EPIDEMIOLOGY
Epidemiology
 Common in India, Indian subcontinents
 Prevalence rate : India, Burma and South Africa : 0 to 1.2%
 In In...
ETIOPATHOGENESIS
ETIOPATHOGENESIS
Local
factors
Chilli
Arecanut
Misi
Systemic
factors
Nutritional
deficiency
Autoimmunity
Genetic
susceptib...
Etiopathogenesis
Capsicum
annum &
capsicum
frutescence
Active extract :
Capsaicin
Vanillylamide
of 8-methyl-6-
noneic acid...
Betel nut
Areca nut –
unhusked
whole fruit of
the areca nut
tree
Betel nut –
inner karnel or
seed which is
obtained after
...
Arecanut
Alkaloids(0.2-0.7%) Flavanoids Others
Arecoline,
Arecaidine
Guvacine
Isoguvacine
Arecolidine
Guvacoline
Tannic ac...
lime
These cause local
irritation and damage to
the mucosa with vesicle
and ulceration on
susceptible individual.
Lime in ...
Tropical Pacific, Asia, and parts of east
Africa.
Etiopathogenesis
 The current production of arecanut in the world is ab...
WHY PEOPLE CHEW ??
Etiopathogenesis
Tobacco
Smoking
form
Smokeless
form
Bidi
Chillum
Chutta
Cigarette
Dhumti
Hookah
Hookli
Khaini
Manipuri Tobacco
Mishri/ Mas...
N’-nitrosonornicotine is produced by bacterial
and enzymatic nitrosation of nicotine and can
be found by reaction of saliv...
Smokeless tobacco
KHAINI
Powdered sun-dried tobacco, slaked
lime (CaOH2) paste mixture
occasionally used with areca nut.
P...
MAINPURI
TOBACCO
CONTAINS : tobacco, slaked lime, finely
cut arecanut, camphor, cloves
Commonly used – Uttar Pradesh
Etiop...
PAAN
Refers to the betel leaf itself – quid
Quid contains : arecanut, lime, aniseed,
cardamom, cinnamon, coconut, cloves, ...
Etiopathogenesis
Misi is a black coloured powder containing various
chemical substances like washing soda, borax, powdered
alum, charcoal o...
Genetic
Predisposition
Collegen-related genes COL1A2, COL3A1,
COL6A1, COL6A3 and COL7A1 have been
identified as targets of...
Nutritional
deficiency
Repeated vesiculations and ulcerations
Vitamin B complex deficiency
Precipitated by the effect of d...
Due to resemblance to scleroderma
Female predominance
Age group
Presence of autoantibodies
Presence of circulatory immune ...
PATHOGENESIS
Normal Oral
MucosaIron and other nutritional
deficiencies
Tobacco, Lime and Betel
nut
Genetic abnormalities
Autoimmunity
H...
2) Molecular Pathogenesis : Collagen Production Pathway (Rajalalitha S, Vali S. 2005)
Pathogenesis
Roberts AB, Flanders KC...
Procollagenase
TGF-ß
Activation of PAI geneActivation of TIMP gene
 PAI
Inhibits activated collagenases
 TIMPs
Plasminog...
BMP- Bone
Morphogenic Protein
PCP- Pro Collagen C
Proteinase
LOX- Lysyl Oxidase
Pathogenesis
Roberts AB, Flanders KC, Kond...
Overall effect of activated TGF –ß Pathway
Increase in collagen
production
Decrease in collagen
degradation
Increase in co...
Increased collagen synthesis (by Arecaidine)
1. Fibroblast proliferation
2. Upregulated collagen genes
3. Upregulation of ...
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 ...
4) Muscle degeneration mechanism - Khanna JN, Andrade NN (1995)
Pathogenesis
Khanna JN, Andrade NN. Oral submucous fibrosi...
5) Role Of Saliva – Salivary Coagulopathy- Chaturvedi VN et al (1991)
Normal mucosa
Slaked Lime Chronic Irritant
Chemical ...
CLINICAL
FEATURES
Clinical features
Sex : both sexes.
Age : Majority of patients : 20-40 years
Sites: buccal mucosa, retromolar areas.
Soft ...
Sunken face appearance
Trismus
Inability to blow
Angular Cheilitis
Clinical features
BLANCHING Clinical features
Reticular blanching
Diffuse blanching
Localized blanching
Labial mucosa
Ventral surfaceDorsal ...
Clinical features
Bud shaped uvula
Restricted tongue movement
Hockey stick appearance of uvula
Depapilated tongue Associat...
MILD/ EARLY PHASE MODERATE PHASE LATE PHASE
 Recurrent stomatitis and
vesiculation (palate)
 Burning sensation to spicy
...
CLASSIFICATION /
GRADING/
STAGING
Classification / Grading/ Staging
More CB, Gupta S, Joshi J, Varma SN. Classification System for Oral Submucous Fibrosis. ...
Classification / Grading/ Staging
Stage I: Stomatitis
and vesiculation
Stage II: Fibrosis
Stage III: As its
sequelae
Class...
Classification based on clinical features of OSMF
Pindborg JJ in 1989
•Stomatitis includes erythematous mucosa, vesicles, ...
Classification based on clinical features of OSMF
Pindborg JJ in 1989
• Sequelae of OSMF are as follows:
• Leukoplakia is ...
Classification based on clinical features of OSMF
SK Katharia et al (1992)
SCORE MOUTH OPENING / INTERINCISAL DISTANCE IN
...
Classification based on clinical features of OSMF
Group A: >35 mm
Group B: Between 30 and 35 mm
Group C: Between 20 and 30...
Classification based on clinical features of OSMF
R Maher et al (1996)
Involvement of one-third or less of
the oral cavity...
Classification based on clinical features of OSMF
Haider et al. (2000)
Clinical staging:
- Stage 1: faucial bands only
- S...
Classification based on clinical features of OSMF
Group I: Only
symptoms, with no
demonstrable
restriction of mouth
openin...
Classification based on clinical features of OSMF
Rajendran R (2003)
EARLY OSF: Burning sensation in the mouth. Blisters
e...
Classification based on clinical features of OSMF
Nagesh and Bailoor (1993)
Stage I early OSMF: Mild blanching, no restric...
Classification based on clinical features of OSMF
Group A—mild cases: Only occasional symptoms, pallor, vesicle formation,...
Classification based on clinical features of OSMF
Stage I: Mouth opening >45 mm
Stage II: Restricted mouth opening 20 to 4...
Classification based on clinical features of OSMF
Chandramani More et al (2011)
Stage 1 (S1)
•Stomatitis and/or
blanching ...
Classification based on clinical features of OSMF
Chandramani More et al (2011)
M1
• Interincisal
mouth
opening up
to or
g...
Prakash R. et al
Based on morphologic variants of soft palate
Type 1: Leaf shaped
Type 2: Rat tail shaped
Type 3: Butt sha...
Classification based on Histopathological features of OSMF
Pindborg JJ and Sirsat SM (1966)
VERY EARLY STAGE:
Finely fibri...
Classification based on Histopathological features of OSMF
Kiran Kumar et al (2007)
1. Grade I: Loose, thick and thin fibe...
HISTOPATHOLOGICAL
FEATURES
Histopathological features
Rooban T, Saraswathi TR, Al Zainab FH, Devi U, Eligabeth J, Ranganathan K. A light microscopic ...
DIFFERENTIAL
DIAGNOSIS
ANEMIC STOMATITIS:
because of presence of
Dysphagia concomitant
with OSMF, patient will
have reduced diet and hence
nutrit...
DIAGNOSIS
Diagnosis
HISTORY OF
BETEL QUID
CHEWING
INTERNATIONAL
CONSENSUS
CRITERIA
LABORATORY
INVESTIGATIONS
 Palpable fibrous band...
Assessment of tongue protrusion
Kumar SM, Shanmugam S. Ramalakshmi M, Jayashankar S. Various treatment modalities and visc...
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 ...
Diagnosis
Assessment of mouth opening
MEAN
INTERINCISAL
DISTANCE
Male: 51.3 mm
(Range 39–65 mm)
Female: 44.3 mm
(Range 36–...
INVESTIGATIONS
INVESTIGATIONS
Hematological & Biochemical
Serological
Cytogenetics
Histopathological
Immunohistochemical
Immunofluorescen...
INVESTIGATIONS
VitaminB 12, folate and
iron
Anaemia
Eosinophilia
serum iron
Decrease in Increase in
total iron-binding
cap...
2) Serological 1. ↑ High-affinity rosette forming cells (HARFC)
2. ↑ Serum levels of IgA, IgD and IgE (Rajendran R
et al- ...
4) Immunohistochemistry 1. ↑ Cytokeratin (CK-2)-
2. ↓CK-17- lalii A et al
3. ↑ Cystatin C - Tsai CH et al -2007
4. ↑ Basic...
MANAGEMENT
MANAGEMENT
Preventiv
e
measures
Medical treatment
Physical
therapy
Surgical
treatment
MANAGEMENT
Preventive measures
Medical treatment
Physical therapy
Surgical treatment
HABIT COUNSELING MANAGEMENT
they’re
patients
MANAGEMENT
Preventive measures
Medical treatment
Physical therapy
Surgical treatment
Antioxidants : b-carotene,
vitamins A, C and E, zinc
Lycopene
Curcumins
Oxitared capsule
Nutrients, Micronutrients and Ant...
IMMUNE
MODULATION
Topical
Betamethasone
Triamcinolone
acetonide
Intralesional
Chymotrypsin
Interferon
gamma (IFN-γ)
Hydroc...
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
ox...
Kelkel M et al. Antioxidant & antiproliferative propertiesv of lycopene. Free radical research, 2011;45(8):925-940.
The an...
Beta carotene
Hydrophobic
molecules with little
or no solubility in
water
Dark green, orange or
yellowish vegetables,
such...
Maintains epithelial integrity
Plays an important role in induction and control of epithelial
differentiation in mucous se...
Zinc
 Epithelializing agent
 Dosage : Zinc sulphate 220mg TDS
 Zinc alone /in combination with vitamin-A better in grad...
Vitamin B complex with iodine (injection
ranodine)
1. I.M -2ml daily
2. Contains
Methyl tri oxyethyl iodomine
Vitamin B1- ...
 Beta carotene- 10mg
 Zinc sulphate monohydrate-27.45mg
 Monohydrated selenium dioxide- 70mcg
 Manganese sulphate- 2mg...
Alpha - lipoic acid is a sulfur-containing substance that is readily converted to and
from its reduced form, dihydrolipoic...
b-carotene, vitamins A, C and E, zinc
Lycopene
Curcumins
Oxitared capsule
Nutrients, Micronutrients and Anti-oxidants
Anti...
Lycopene ANTIOXIDANTS
 Lycopene is a bright red
carotenoid pigment.
 Its name is derived from the
tomato's species class...
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. L...
b-carotene, vitamins A, C and E, zinc, copper, manganese and
selenium
Lycopene
Curcumins
Spirulina
Oxitared capsule
Nutrie...
ANTIOXIDANTS
Das D, Balan A, Sreelatha KT. Comparative Study of the Efficacy of Curcumin and Turmeric Oil as Chemopreventi...
Antioxidants (b-carotene, vitamins A, C and E,
zinc, copper, manganese and selenium)
Lycopene
Curcumins
Oxitared capsule
N...
Contents
 Amra (Mangifera Indica)
 Ashwagandha (Withania Somnifera)
 Garjara (Daucus Carota)
 Yashtimadhu (Glycyrrhiza...
Biogenic stimulation
Placental extract
Proteolytic enzymes
• Collagenase
• Hyaluronidase
Biogenic stimulation
PLACENTAL EXTRACT
Proteolytic enzymes
• Collagenase
• Hyaluronidase
Placental extract
Placentrex was first introduced By Flator(1933) and later developed
in 1953. It owes its inception to co...
1. Nucleotides –RNA , DNA, ATP
2. Enzymes –
a. Alkaline & acid phosphatase,
b. Glutammic Oxalo-acetic acid
c. Transaminase...
DOSE
•2 ml of solution deposited at interval of 3 days for in
divided region.
•This course can be repeated after a month i...
Biogenic stimulation
PLACENTAL EXTRACT
Proteolytic enzymes
• Collagenase
• Hyaluronidase
COLLAGENASE
The collagenase treatment not only resulted in a significant
improvement of oral opening, but patients also ex...
Biogenic stimulation
PLACENTAL EXTRACT
Proteolytic enzymes
• Collagenase
• Hyaluronidase
HYALURONIDASE
(HYALASE)
Mechanism
Fibrinolytic
enzyme
It helps in
breakdown
hyaluronic
acid
Lower
viscosity of
the
interce...
IMMUNE
MODULATION
Topical
Betamethasone
Triamcinolone
acetonide
Intralesional
Chymotrypsin
Interferon
gamma (IFN-γ)
Hydroc...
Corticosteroids
Topical
•Triamcinalone
acetonide 0.1%
(Kenacort)
•Betamethasone – 0.5%
(Betnesol)
Intralesional
•Dexametha...
 Chymotrypsin, an endopeptidase, hydrolyzes ester and peptide bonds,
thus acting as a proteolytic and anti-inflammatory a...
INTERFERON GAMMA
 Downregulates fibroblast proliferation and collagen synthesis
 Upregulates the anti-fibrotic cytokines...
LEVAMISOLE
 Anthelminthic and Immunomodulator
 50 mg three times daily for three alternate weeks
 Levamisole can bring ...
Immune milk is a
kind of skimmed
milk produced from
cows immunised
with multiple
human intestinal
bacteria.
It has good an...
1. Pentoxifylline
2. Nylidrin hydrochloride
Promotion of blood
flow
1. Pentoxifylline
2. Nylidrin hydrochloride
Promotion of
blood flow
Actions
• Improves microcirculation
• Decreases plate...
Betel quid chewing habit
Chronic inflammatory
process
TGF-
Collagen production
1. Anti-inflammatory /
immuno-modulatory d...
The most commonly used combination:
 Chymotrypsin (5000 IU),
 Hyaluronidase (1500 IU)
 dexamethasone (4 mg)
 Physiothe...
COMBINATIONS
OSMF with trismus be treated by 1.5 ml (37.5 mg) hydrocortisone acetate mixed with 1500
IU of hyaluronidase ...
MANAGEMENT
Preventive measures
Medical treatment
Physical therapy
Surgical treatment
Laser
Muscle stretching exercises
Diathermy
Ultrasound
Physical therapy
Muscle stretching exercises for the mouth
includes forceful mouth opening with the
help of sticks, ballooning of mouth, ho...
A man diagnosed with OSMF
(mouth opening at interincisal
level: 34 mm), was treated with
the MED ,followed every month
for...
Diathermy
Low current of 2450 cycles x 20 watts is given.
The mechanism involved is Physiofibrinolysis.
Effective, if it i...
The ErCr:YSGG (waterlase C-
100) laser was used to release
the fibrotic bands of OSMF
that were causing limited
mouth open...
Ultrasound treatment accelerate healing, increase the
extensibility of collagen fibers, provide pain relief and
selectivel...
MANAGEMENT
Preventive measures
Medical treatment
Physical therapy
Surgical treatment
Motawetz G.1987.-
Excision of fibrotic
bands with sub-
mucosal placements
of human skin grafts.
Gupta and sharma et
al 198...
Surgical striping of fibrous bands
Partial thickness skin or mucosal grafts
Buccal pad of fat interposition
Myotomy
Bilate...
MALIGNANT
POTENTIAL
Malignant Potential
Paymester –first person to see malignant changes in
OSMF
Pindborg JJ et al (1984) : 4.5%
Murti PR et a...
Hyperkeratosis
intercellular edema in the
prickle
cell layers and the basal cells
Hyperplasia
Excessive fibrosis  Ischaem...
PROGNOSIS
Oral submucous Fibrosis being an irreversible condition has no
effective treatment. Early diagnosis, and treatment and eli...
CONCLUSION
Koneru A, Hunasgi S, Hallikeri K, Surekha R, Nellithady GS, Vanishree M. A systematic review of various treatment
modaliti...
REFERENCES
1. Inderbir Singh.Textbook of Human Histology 5th edition Jaypee Brothers Medical Publishers;2009.
2. //www.google.co.in/s...
11. Chaturvedi VN, Sharma AK, Chakrabarati S. Salivary coagulopathy and humoral response in oral
submucous fibrosis. JIDA ...
19. Lingappa A, Nappalli D, Sujatha GP, Shiva Prasad S. Areca nut: to chew or not to chew? e-Journal of
Dentistry July - S...
REFERENCES
27. Rajendran R. Oral submucous fibrosis, etiology, pathogenesis and future research. Bull World Health
Organ 1...
37. Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of
potentially malignant disorders of t...
44. Greenberg MS, Glick M, Ship JA. Burket’s Oral Medicine. 11th ed. India: BC Decker Inc;
2008.
45. Ali FM, Prasant MC, P...
52. Vijayakumar M, Priya D. Physiotherapy for improving mouth opening & tongue protrution in patients with Oral
Submucous ...
Thank you
Oral Submucous Fibrosis - OSMF : Dr Sanjana Ravindra
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Oral Submucous Fibrosis - OSMF : Dr Sanjana Ravindra

Introduction
History
Definition
Epidemiology
Nomenclature
Etiopathogenesis
Clinical features
Classification
Histopathology
Differential diagnosis
Diagnostic Criteria
Investigations
Management
Malignant Potential
Prognosis
Conclusion
References

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Oral Submucous Fibrosis - OSMF : Dr Sanjana Ravindra

  1. 1. Oral Submucous Fibrosis Dr Sanjana Ravindra Post Graduate RajaRajeswari dental College, Bangalore.
  2. 2. CONTENTS  Introduction  History  Definition  Epidemiology  Nomenclature  Etiopathogenesis  Clinical features  Classification  Histopathology  Differential diagnosis  Diagnostic Criteria  Investigations  Management  Malignant Potential  Prognosis  Conclusion  References
  3. 3. INTRODUCTION
  4. 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. 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. 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. 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. 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. 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
  10. 10. DEFINITION
  11. 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. 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. 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.
  14. 14. HISTORY
  15. 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. 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
  17. 17. SYNONYMS
  18. 18. 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 submucous fibrosis. Quality in Primary Care (2015) 23 (6): 327-332
  19. 19. EPIDEMIOLOGY
  20. 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%
  21. 21. ETIOPATHOGENESIS
  22. 22. 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.
  23. 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. 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
  25. 25. 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)
  26. 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. 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
  28. 28. WHY PEOPLE CHEW ?? Etiopathogenesis
  29. 29. Tobacco Smoking form Smokeless form Bidi Chillum Chutta Cigarette Dhumti Hookah Hookli Khaini Manipuri Tobacco Mishri/ Masheri Paan Snuff Gudhaku Zarda 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’
  30. 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. 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
  32. 32. MAINPURI TOBACCO CONTAINS : tobacco, slaked lime, finely cut arecanut, camphor, cloves Commonly used – Uttar Pradesh Etiopathogenesis
  33. 33. PAAN Refers to the betel leaf itself – quid Quid contains : arecanut, lime, aniseed, cardamom, cinnamon, coconut, cloves, sugar, tobacco wrapped in betel leaf. Etiopathogenesis
  34. 34. Etiopathogenesis
  35. 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. 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. 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. 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.
  39. 39. PATHOGENESIS
  40. 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. 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. 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. 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. 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. 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. 46. Pathogenesis Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.
  47. 47. Pathogenesis Angadi PV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaci Surg(2011) : 15:1 – 9.
  48. 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. 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. 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.
  51. 51. CLINICAL FEATURES
  52. 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
  53. 53. Sunken face appearance Trismus Inability to blow Angular Cheilitis Clinical features
  54. 54. BLANCHING Clinical features Reticular blanching Diffuse blanching Localized blanching Labial mucosa Ventral surfaceDorsal surface Gingiva
  55. 55. Clinical features Bud shaped uvula Restricted tongue movement Hockey stick appearance of uvula Depapilated tongue Associated with premalignancy
  56. 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
  57. 57. CLASSIFICATION / GRADING/ STAGING
  58. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.
  76. 76. HISTOPATHOLOGICAL FEATURES
  77. 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.
  78. 78. DIFFERENTIAL DIAGNOSIS
  79. 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
  80. 80. DIAGNOSIS
  81. 81. Diagnosis HISTORY OF BETEL QUID CHEWING INTERNATIONAL CONSENSUS CRITERIA LABORATORY INVESTIGATIONS  Palpable fibrous bands  Mucosal texture feels tough & leathery  Blanching of mucosa together  Decreased Hb, iron, protein and vitamin B complex levels  Increased erythrocyte sedimentation rate
  82. 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. 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. 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.
  85. 85. INVESTIGATIONS
  86. 86. INVESTIGATIONS Hematological & Biochemical Serological Cytogenetics Histopathological Immunohistochemical Immunofluorescence Tissue Culture
  87. 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. 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. 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
  90. 90. MANAGEMENT
  91. 91. MANAGEMENT Preventiv e measures Medical treatment Physical therapy Surgical treatment
  92. 92. MANAGEMENT Preventive measures Medical treatment Physical therapy Surgical treatment
  93. 93. HABIT COUNSELING MANAGEMENT they’re patients
  94. 94. MANAGEMENT Preventive measures Medical treatment Physical therapy Surgical treatment
  95. 95. 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
  96. 96. IMMUNE MODULATION Topical Betamethasone Triamcinolone acetonide Intralesional Chymotrypsin Interferon gamma (IFN-γ) Hydrocortisone Betamethasone Methylprednisol one Triamcinolone diacetate Dexamethasone Systemic Levamisole Immune milk Colchine 1. Pentoxifylline 2. Nylidrin hydrochloride Promotion of blood flow
  97. 97. b-carotene, vitamins A, C and E, zinc Lycopene Curcumins Oxitared capsule Nutrients, Micronutrients and Anti-oxidants
  98. 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. 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. 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. 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. 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. 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
  104. 104.  Beta carotene- 10mg  Zinc sulphate monohydrate-27.45mg  Monohydrated selenium dioxide- 70mcg  Manganese sulphate- 2mg  Copper sulphate- 1mg ANTIOXIDANTS COMBINATIONS Antoxid (Capsule) ANTIOXIDANTS
  105. 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. 106. b-carotene, vitamins A, C and E, zinc Lycopene Curcumins Oxitared capsule Nutrients, Micronutrients and Anti-oxidants Antioxidants
  107. 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. 108. Agarwal A,Roa A .Tomato lycopene and its role in human health & chronic diseases . CMAJ.2009;163(6) Lycopene
  109. 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. 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. 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. 112. Antioxidants (b-carotene, vitamins A, C and E, zinc, copper, manganese and selenium) Lycopene Curcumins Oxitared capsule Nutrients, Micronutrients and Anti-oxidants
  113. 113. Contents  Amra (Mangifera Indica)  Ashwagandha (Withania Somnifera)  Garjara (Daucus Carota)  Yashtimadhu (Glycyrrhiza Glabra)  Draksha (Vitis Vinifera)  Amalaki (Emblica officinalis)  Lavanga (Syzygium Aromaticum ) ANTIOXIDANTS Oxitard Doses 2 capsules twice daily for period of 3 month
  114. 114. Biogenic stimulation Placental extract Proteolytic enzymes • Collagenase • Hyaluronidase
  115. 115. Biogenic stimulation PLACENTAL EXTRACT Proteolytic enzymes • Collagenase • Hyaluronidase
  116. 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. 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. 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
  119. 119. Biogenic stimulation PLACENTAL EXTRACT Proteolytic enzymes • Collagenase • Hyaluronidase
  120. 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).
  121. 121. Biogenic stimulation PLACENTAL EXTRACT Proteolytic enzymes • Collagenase • Hyaluronidase
  122. 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.
  123. 123. 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
  124. 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. 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. 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. 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. 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.
  129. 129. 1. Pentoxifylline 2. Nylidrin hydrochloride Promotion of blood flow
  130. 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. 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. 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. 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.
  134. 134. MANAGEMENT Preventive measures Medical treatment Physical therapy Surgical treatment
  135. 135. Laser Muscle stretching exercises Diathermy Ultrasound Physical therapy
  136. 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. 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. 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. 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. 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
  141. 141. MANAGEMENT Preventive measures Medical treatment Physical therapy Surgical treatment
  142. 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. 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
  144. 144. MALIGNANT POTENTIAL
  145. 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. 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
  147. 147. PROGNOSIS
  148. 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
  149. 149. CONCLUSION
  150. 150. 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
  151. 151. REFERENCES
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