oral submucous fibrosis

1. Oral SubmucouS FIBROSIS
(Emphasis on Medical
Management)
HOD Oral Medicine & Diagnostics.
Assistant Professor
Dr. Muhammad Adeel
BDS,MCPS(ORAL SURGERY)

2. Learning Objectives:
• A brief introduction to the disease.
• Definition of the Oral submucous fibrosis.
• Epidemiology of the disease.
• Etiopathogenesis of Oral submucous fibrosis.
• Clinical features that suggest to diagnose OSF.
• Classification or Staging/grading of OSF.
• Various medical treatment options available for OSF.
• Conclusion.

3. Oral Mucous Membrane……
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 even premalignant or malignant changes as well.

4. Difference between PRE-MALIGNANT LESION
& PRE-MALIGNANT CONDITION.
• PRE-MALIGNANT LESION
“A morphologically altered tissue in which oral cancer is more likely to occur than in
its apparently normal counterpart”
e.g, Leukoplakia, erythroplakia etc.
• PRE-MALIGNANT CONDITION
“A generalized state associated with a significantly increased risk of cancer”
e.g, Oral submucous fibrosis, Oral lichen planus etc.
World Health Organization. Report of a meeting of investigators on the histological definition of precancerous lesions. Geneva: World Health Organization;
1973 Can 731.

5. History of Oral Submucous Fibrosis
First described among five East
African women of Indian origin
under the term Atrophia
idiopathica Mucosae Oris by
Schwartz in 1952
Joshi in 1952 is credited to be the
first person who described it and
gave the present term
“Oral sub-mucous fibrosis”
Ahuja SC and Ahuja U. Betel Leaf and Betel Nut in India: History and Uses. Asian Agri-History 2011;15(1):13–35.

6. Definition of Oral Submucous Fibrosis:
“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)
World Health Organization Collaborating Centre for Oral Precancerous lesions. Definition of leukoplakiaand related lesions: an aid to studies on
oral precancer. Oral SurgOral Med Oral Pathol1978; 46: 518–39.

7. Epidemiology of Oral Submucous Fibrosis:
Common in India, Indian subcontinents
High in southern parts of India, where the incidence of
oral cancer is also high.

8. Etiopathogenesis of Oral submucous fibrosis:
Local factors:
Betel Nut/Areca Nut chewing.
Tobacco.
Chilli.
Systemic factors:
Nutritional deficiency.
Autoimmunity.
Genetic susceptibility.
RajendranR.: Oral submucousfibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.

9. Local Factors:
Betel Nut/Areca Nut
Ingredients commonly used in the preparation of betel quid
 Betel leaf (also known as pan)
 Areca nut (supari) seed of areca catechu tree
 Lime (calcium hydroxide)
 Catechu (resinous extract from acacia tree)
 Tobacco
LingappaA, NappalliD, SujathaGP, Shiva Prasad S. Areca nut: to chew or not to chew? e-Journal of Dentistry July -Sep 2011 Vol1 Issue 3

11. Local Factors:
Chillies
Capsicum annum &
capsicum frutescence
Active extract : CapsaicinVanillylamide
of 8-methyl-6-
noneic acid
• 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 significant
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 in take.)

12. Local Factors:
Tobacco

13. Systemic Factors:
Genetic
Predisposition
Collagen-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
BasoyaS. Etiopathogenesisand management of oral submucousfibrosis. Quality in Primary Care
(2015) 23 (6): 327-332

14. Systemic Factors:
Nutritional
deficiency
• Vitamin B complex deficiency
• Iron deficiency anemia
Repeated vesiculations and ulcerations
RajendranR.: Oral submucousfibrosis: etiology, pathogenesis and future research. Bulletin of
World Health Organisation, 2009;72 (6): 985-996.

15. Systemic Factors:
Autoimmunity
Betal nut can act as heptens to produce auto-antibodies to oral mucosal
cells.
RajendranR.: Oral submucousfibrosis: etiology, pathogenesis and future research. Bulletin of World
Health Organisation, 2009;72 (6): 985-996.

16. PATHOGENISIS

17. ARECA NUT
Arecoline Arecaidine
HYDROLYSIS
Up-regulation of
collagen synthesis
genes
COL1A1 , COL3A1 etc
Increase pro-fibrotic
cytokines like
IL-1 , IL-6
TGF-ß
Gene Polymorphism
as
TGF-ß
Over all effect of TGF-ß
AngadiPV, Rao SS. Areca nut in pathogenesis of OSMF: Revisited. Oral maxillofaciSurg(2011) : 15:1 –9.

18. CLINICAL FEATURES
of OSF

19. Sex : both sexes.
Age : Majority of patients : 20-40 years
Sites:
 Buccal mucosa
 Retro molar areas.
 Soft palate
 Palatal fauces
 Uvula
 Tongue
 Labial mucosa
 Floor of mouth and gingiva
Pindborg : Oral submucousfibrosis: etiology, pathogenesis and future research. Bulletin of World Health Organisation, 2009;72 (6): 985-996.

20. Angular Cheilitis Inability to blow
Sunken face appearance Trismus
Mubeen. White lesions. In: VenkataramanBK. Diagnostic Oral Medicine.1st ed. Haryana: WoltersKluwer Health; 2013. p. 91-99

21. BLANCHING
Localized blanching Reticular blanching Dorsal surface Ventral surface
Diffuse blanching Labial mucosa
Gingiva
Mubeen. White lesions. In: VenkataramanBK. Diagnostic Oral Medicine.1st ed. Haryana: WoltersKluwer Health; 2013. p. 91-99

22. Depapilated tongue Restricted tongue movement Associated with pre-malignancy
Mubeen. White lesions. In: VenkataramanBK. Diagnostic Oral Medicine.1st ed. Haryana: WoltersKluwer Health; 2013. p. 91-99

23. Other clinical features include,
• Fibrous bands on buccal mucosa and lips.
( longitudinal bands on buccal mucosa and circular bands on
• lips)
• Change of taste
• Dryness of mouth
• Ear ache
• Loss of hearing, due to stenosis of Eustachian tubes
• Recurrent ulceration
• Reduced movement of soft palate
• Shrinking of the uvula
Mubeen. White lesions. In: VenkataramanBK. Diagnostic Oral Medicine.1st ed. Haryana: WoltersKluwer Health; 2013. p. 91-99

24. CLASSIFICATION /
GRADING/ STAGING

25. STAGE 1: STOMATITIS
In this stage, the
mucous membrane of the mouth
is inflamed.
STAGE 2: FIBROSIS
This is marked by the development of
lesions in the mouth, oral mucosa
blanching as well as circular and
vertical palpable fibrous patches in and
around the mouth. This gives a mottled
appearance to the buccal mucosa.
STAGE 3: SEQUELAE OF OSF
It is identified by the presence of
Leukoplakia and various speech
and hearing difficulty
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

26. 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
Haideret al. (2000)
HaiderSM, Merchant AT, FikreeFF, RahbarMH. Clinical and functional staging of oral submucous fibrosis. Br
JOralMaxillofacSurg.2000 Feb;38(1):12-5.

27. MANAGEMENT

29. Includes,
a) Nutrients/Micro-nutrients:
Anti-oxidants ( ß-carotene , Vit.A , Vit.E and Zinc)
Lycopene.
b) Biogenic Stimulants:
Placental Extract.
c) Immune modulators:
Topical, Systemic and intra-lesional corticosteroids.
d) Blood flow promotors:
Pentoxifylline.

30. ANTIOXIDANTS
Antioxidants are protective agents that inactivate reactive
oxygen species and therefore significantly delay or prevent
oxidative damage.

31. Beta carotene , vitamin A & vitamin E
Hydrophobic molecules with little or no solubility in water
SOURCES:
Dark green, orange or yellowish vegetables, such as spinach,
carrots, sweet potato, mango, papaya, and oranges etc.
• Vitamin A 50,000 IU orally daily (12Weeks)
• Cap. Evion 400mg (one cap. Daily for 12 weeks)
KelkelM et al. Antioxidant & antiproliferativepropertiesvof lycopene. Free radical research, 2011;45(8):925-940.

32. Zinc:
• Epithelializing agent
• Dosage: Zinc sulphate 20 mg TDS for 1 month.
• Zinc alone/in combination with vitamin-A better in stage I & II
• Zinc + cortisone effective in stage III
Availibility:
1) Tab.Zinxus 20mg
2) Tab.Orazinc 20mg
Rui L et al Lycopene: features and potential significance in the oral cancer and precancerous lesions J Oral Pathol Med 2011;40: 361–368

33. Lycopene
 Lycopene is a bright red carotenoid pigment.
 Its name is derived from the tomato's species.
SOURCES: Tomatoes, watermelons, guava,red chilli
Tomato & tomato-based food –85%
BENEFITS ON HUMAN HEALTH
• AO activity
• Interference with growth factor stimulation
• Inhibition of cancer cell proliferation
DOSES : A) 16 mg of lycopene daily in 2 equally divided doses. Kumar A et al, 2007
B) 2000 μg of lycopene twice daily for 3 month. Gowda Betal ,2011
Rao A.V., Ray M.R, Rao L.G. Lycopene .Advances in food and nutrition research. 2006 3(51):100-164

34. Biogenic Stimulants:
Placental extract:
Placentrex was first introduced By Flator (1933) and later developed in 1953.
ACTIONS OF PLACENTREX
• Stimulates regenerative process.
• Increase physiological function of organs.
• Has anti-inflammatory effect
Available in 4 forms
• Aqueous solution of human placenta
• Lipoid extracts
• Immuno-gamma globulins
• Tissue coagulants
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.
Thakur.Get al.DoesTopical Application of Placental Extract Gel on Postoperative FibrotomyWound
Improve Mouth Opening and Wound Healing in Patients With Oral SubmucousFibrosis?
J.oralmax.surg.july.2015. 1439.e1–1439.e10

35. Immune modulators:
a) Topical Betamethasone
Triamcinolone acetonide
b) Intralesional Hydrocortisone
Betamethasone
Methylprednisolone
Triamcinolone diacetate
Dexamethasone
c) Systemic Immune milk
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)Kerr AR et al. A systematic review of medical interventions for oral submucousfibrosis and
future research opportunities. Oral Diseases (2011) 17 (Suppl. 1), 42–57.

36. Blood flow promotors:
Pentoxifylline: (Tab.Agapurin 400mg)
Actions
Fibrinolytic activity (main action for OSMF)
DOSES
Pentoxifylline: 400 mg 3 times a day for 7 months
Side-effects
•GIT- Nausea, vomiting,
•CNS- Dizziness , Headache
RajendranR, Rani V, Shaikh S. Pentoxifyllinetherapy : A new
adjunct in the treatment of oral submucousfibrosis. Indian J Dent
Res [2013];17:190-8.

37. CONCLUSION

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