3. DEFINITION
It is an insidious chronic disease affecting any part of
the oral cavity and sometimes the pharynx. Although
occasionally preceded by and /or associated with
vesicle formation ,it is always associated with juxtaepithelial inflammatory reaction followed by a fibroelastic changes of the lamina propria with epithelial
atrophy leading to stiffness of the oral mucosa and
causing trismus and inability to eat.
(J.J Pindborg and Sirsat 1966)
4. HISTORY
The condition of oro -pharyngeal OSMF of oral cavity
was prevalent even in the days of Shushrutha (600
B.C).
Shushrutha, the greatest practitioner of ancient
medicine stated in his book "Shushrutha Samhita' a
condition called 'VIDARI' in his classification of
diseases of mouth and throat.
The features of which suit the symptomatology of
OSMF.
5.
First described among five East African women of
Indian origin under the term Atrophia idiopathica
(tropica) Mucosae Oris by Schwartz 1952
Joshi in 1953 is credited to be the first person who
described it and gave the present term “Oral submucous fibrosis”.
In the year 1954, Su. P. from Taiwan described similar
condition, which he called "Idiopathic Scleroderma of
mouth"
6. KEY WORDS
Quid has been defined as 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 (Zain et al., 1999).
A precancerous lesion is a morphologically altered
tissue in which oral cancer is more likely to occur
than in its apparently normal counterpart‟;
A precancerous condition is a generalized state
associated with a significantly increased risk of
cancer‟.
J Cancer Science & Therapy - Volume 1(2) : 072-077 (2009) - 075
8. The major areca nut alkaloids are arecoline, arecadine,
arecolidine, guyacoline and guacine.
The important flavonoid components in areca nut are
tannins and catechins.
These alkaloids undergo nitrosation and give rise to Nnitrosamine which may have cytotoxic effect on cells.
(Hoffmann et al., 1994)
Betel quid is placed in the buccal vestibule for ~15 min
to 1 hr & repeated 5-6 times a day which leads to
constant contact between mixture & mucosa.
The alkaloids from the quid are absorbed into the
mucosa and undergoes metabolism.
Microtrauma produced by the friction of coarse fibers of
areca nut also facilitates diffusion of the alkaloids into
the subepithelial connective tissue resulting in
juxtaepithelial inflammatory cell infiltration. (Chiang et
al., 2002).
9. Oral mucosa
Betel quid
Constant irritation
Chronic inflammation
Activated T cell and macrophages at the site
Increase in cytokines IL 6, TNF, Ifa, increase in growth factor TGFβ
11. COLLAGEN PRODUCTION PATHWAY
3 main events in this pathway activation of
procollagen, elevation of procollagen proteinase levels,
and upregulation of lysyl oxidase (LOX activity).
The genes COL1A2, COL3A1, COL6A1, COL6A3,
COL7A1 have been identified as definitive TGF-β
targets. (Rajalalitha & Vali, 2005).
Yi-Ting et al., 2009, found arecoline stimulated CTGF
production in buccal mucosal fibroblasts (BMFs)
12. UP-REGULATION OF LOX
The Cu content of areca nut is high & levels of
soluble Cu in saliva may rise in volunteers who
chew areca quid (Trivedy et al, 1997).
The enzyme Lysyl oxidase (LOX) is found to be
upregulated in OSMF.
The fibroblast in OSMF have not only increased
LOX activity but also specific growth characteristics.
This was evident with the reported cell doubling
time of 3.2 days for OSMF & 3.6 days for normal
fibroblasts (Ma et al., 1995).
13. “The Evaluation of serum copper & iron levels among
oral submucous fibrosis patients.”
50 cases and controls each were each tested for
serum copper & iron levels.
Conclusion: Copper levels increased & iron levels
decreased in study group in comparison to healthy
controls. Copper levels increased as clinical stage of
oral submucous fibrosis increased.
Tadakamadla J, Kumar S, Mamatha GP. Med Oral
Patol Oral Cir Bucal. 2011: 1; 16(7); e870-3.
14. COLLAGEN DEGRADATION PATHWAY
2 main events modulated by TGF which decreases
the collagen degradation are:
Activation of inhibitor of matrix metalloproteinase
gene TIMPs
Activation of plasminogen activator inhibitor PAI
gene.
15. PRECANCEROUS NATURE & MALIGNANT
TRANSFORMATION
First described by Paymaster in 1956.
Pindborg et al., 1984, put forward 5 criteria to prove
disease to be precancerous. These include, high
occurrence of OSMF in oral cancer patients, higher
incidence of SCC in patients with OSMF, histological
diagnosis of cancer without any clinical suspicion in
OSMF, high frequency of epithelial dysplasia and higher
prevalence of leukoplakia among OSMF.
Malignant transformation rate of OSMF was found to be
the range of 7-13%.
16. Areca nut/Betel nut
Mechanical trauma
to epithelium
Carcinogen acts as antigen
to keratinocytes
Carcinogen reaches
basal zone & affects
stem cells
Stem cells produce
iNOS
DNA DAMAGE
TGF-β
FGF
Stem cell
hypoproliferation
(Epithelial hypoplasia)
Sustained
DNA DAMAGE
Loss of rete
ridges
Dysplasia
Subepithelial
hyalinization
17. “Estimation of serum beta carotene levels in patients
with oral submucous fibrosis in India.”
45 cases & controls each were evaluated for their
serum beta carotene levels.
Results: Mean serum beta carotene levels were
found to be lower for cases than controls.
They concluded that beta carotene plays an important
role in the pathogenesis of OSMF, and that its level
decreases with disease progression.
Aggarwal A, Shetti A, Keluskar V, Bagewadi A. J Oral
Sci. 2011: 53(4); 427-431.
19. Progressive inability to open the mouth(trismus)
due to oral fibrosis & scarring.
Oral pain & a burning sensation upon consumption
of spicy foodstuffs.
Increased salivation
Change of gustatory sensation
Hearing loss due to stenosis of the eustachian
tubes
Dryness of the mouth
Nasal tonality to the voice
Dysphagia to solids (if esophagus is involved)
Impaired mouth movements
20. Intra-oral view showing: A. Marble-like appearance of soft palate, faucial pillars &
upper pharyngeal mucosa B. shrunken uvula, blanching of left buccal mucosa &
retromolar region, C. Fibrosis & depapillation of tongue, D. Blanching of right
buccal mucosa, E. Fibrosis & pigmentation of lower lip
23. Decreased hemoglobin levels
Decreased iron levels
Decreased protein levels
Increased erythrocyte sedimentation rate
Decreased Vitamin B complex levels
24. “Lipid profile in oral submucous fibrosis”
65 clinically diagnosed and histopathologically proven patients of
OSMF and 42 age and sex matched controls were studied. In
these samples serum lipids including: (i) Total cholesterol, (ii) LDL
cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL
cholesterol (VLDLC) (v) triglycerides (vi) Apo-A1 (viii) Apo-B and
(viii) LPa were analyzed.
A significant decrease in plasma total cholesterol, HDLC and ApoA1 was observed in patients with OSMF as compared to the
controls. Thus an inverse relationship between plasma lipid levels
and patients was found in OSMF.
Mehrotra R et al. Lipids in Health and Disease. 2009; 8: 29
25. STAGING
More CB et al. Classification system for Oral
submucous fibrosis. JIAOMR. 2012; 24(1): 24-29.
26. Pindborg JJ, 1989
Stage I: Stomatitis includes erythematous mucosa, vesicles, mucosal
ulcers, melanotic mucosal pigmentation & mucosal petechiae.
Stage II: Fibrosis occurs in healing vesicles & ulcers, which is the hallmark
of this stage.
- Early lesions show blanching of the oral mucosa.
- Older lesions include vertical & circular palpable fibrous bands in the
buccal mucosa & around the mouth opening or lips.
- This results in a mottled marble like appearance.
- Specific findings include reduction of mouth opening, stiff & small
tongue, blanched & leathery floor of the mouth, fibrotic & depigmented
gingiva, rubbery soft palate with decreased mobility, blanched &
atrophic tonsils, shrunken bud-like uvula & sunken cheeks not
commensurate with age or nutritional status.
Stage III: Sequelae of OSMF are as follows:
- Leukoplakia is found in more than 25% of individuals with OSMF.
- Speech & hearing deficit may occur because of involvement of tongue &
eustachian tube.
27. Nagesh & Bailoor (1993)
Stage I early OSMF: Mild blanching, no restriction in mouth
opening (normal distance between central incisor tips:
Males 35-45 mm, females 30-42 mm), no restriction in
tongue protrusion, cheek flexibility. Burning sensation on
taking spicy food or hot beverages.
Stage II moderate OSMF: Moderate to severe blanching,
mouth opening reduced by 33%, cheek flexibility also
demonstrably reduced, burning sensation also in absence
of stimuli, palpable bands felt. Lymphadenopathy either
U/L or B/L, anemia on hematological examination.
28. Khanna JN & Andrade NN (1995)
Group I:
- Very early cases: burning sensation in the mouth, acute
ulceration & recurrent stomatitis & not associated with
mouth opening limitation.
- Histology: Fine fibrillar collagen network interspersed with
marked edema, blood vessels dilated & congested, large
aggregate if plump young fibroblasts present with
abundant cytoplasm, inflammatory cells mainly consist of
PMNs with few eosinophils. The epithelium is normal.
29. Khanna JN & Andrade NN (1995)
Group II:
- Early cases: Buccal mucosa appears mottled & marble
like, widespread sheets of fibrosis palpable, interincisal
distance of 26 to 35 mm.
- Histology: Juxta-epithelial hyalinization present, collagen
present as thickened but separate bundles, blood vessels
dilated & congested, young fibroblasts seen in moderate
number, inflammatory cells mainly consist of PMNs with
few eosinophils & occasional plasma cells, flattening
or shortening of epithelial rete-pegs evident with
varying degree of keratinization.
30. Khanna JN & Andrade NN (1995)
Group III:
- Early cases: Moderately advanced cases- Trismus,
interincisal distance of 15-25 mm, buccal mucosa appears
pale firmly attached to underlying tissues, atrophy of
vermilion border, vertical fibrous bands palpable at the soft
palate, pterygomandibular raphe & anterior faucial pillars.
- Histology: Juxta-epithelial hyalinization present, thickened
collagen bundles, residual edema, constricted blood
vessels, mature fibroblasts with scanty cytoplasm &
spindle-shaped nuclei, inflammatory exudate which
consists of lymphocytes & plasma cells, epithelium
markedly atrophic with loss of rete pegs, muscle fibers
seen with thickened dense collagen fibers.
31. Khanna JN & Andrade NN (1995)
Group IVA:
- Advanced cases- severe trismus, interincisal distance of
less than 15 mm, thickened faucial pillars, shrunken
uvula, restricted tongue movement, presence of circular
band around entire lip & mouth.
Group IVB:
- Advanced cases- presence of hyperkeratotic leukoplakia
&/or squamous cell carcinoma.
-
Histology: Collagen hyalinized smooth sheet, extensive fibrosis,
obliterated the mucosal blood vessels, eliminated melanocytes,
absent fibroblasts within the hyalinized zones, total loss of epithelial
rete pegs, presence of mild to moderate atypia & extensive
degeneration of muscle fibers.
33. TREATMENT
Taneja L, Nagpal A, Vohra P, Arya V. Oral submucous
Fibrosis: An oral physician approach. J Innov Dent
2011; 1(3)
34. DISCONTINUATION OF HABIT & COUNSELING
Encouraged through education & advocacy.
Patient should be explained about the disease & its
possible malignant potential.
Thorough counseling should be given for deaddiction.
35. SUPPORTIVE CARE
Vitamins, iron & mineral rich diet should be advised
to patients with OSMF.
Intake of red tomatoes, fresh fruits & green leafy
vegetables should be included in the regular diet.
Green tea should be included in the diet chart.
Routine Hb levels followed by iron supplements
should be included in treatment plan.
36. “The Response of Oral Submucous Fibrosis to
Lycopene – A Carotenoid Antioxidant: A
Clinicopathological Study”
2000µg of Lycopene capsule was given orally twice daily
for 3 months to 12 patients.
Clinical and histological improvement was seen in various
parameters used in the study.
Gowda BBK et al. JCDR. 2011
37. MEDICAL MANAGEMENT
STEROIDS:
Inhibit proliferation of fibroblasts.
Release cellular proteases in the connective tissue
extracellular compartment.
Inhibit the inflammatory response.
38. HYALURONIDASE
Reduces burning sensation & trismus.
Acts by breaking down hyaluronic acid, lowers the
viscosity of intracellular substances.
Decreases collagen formation.
“The combination of steroids & hyaluronidase
shows better long-term results than either agent
used alone.” (Kakar, 1985).
39. “Efficacy of hydrocortisone acetate/hylauronidase vs
triamcinolone acetonide/hyaluronidase in the
treatment of oral submucous fibrosis” was evaluated.
1 group received hydrocortisone acetate (1.5 ml)/
hyaluronidase (1500 IU) weekly while other received
triamcinolone acetonide (10 mg/ml)/hyaluronidase
(1500 IU) at 15 days interval for 22 weeks.
No statistically significant difference was seen in both
groups.
Treatment regimen B was more convenient because
of lesser visits & less cost.
Indian J Med Res 2010:131;6655-669.
40. PLACENTAL EXTRACTS
It is an aqueous extract of human placenta that
contains nucleotides, enzymes, vitamins,
aminoacids & steroids.
It acts by “Biogenic stimulation”.
Its use is based on the method of “tissue therapy”
introduced by Filatov in 1933.
No contraindications & the results are found to be
lasting.
42. INTERFERON-GAMMA
Has immuno-regulatory effect, is a known antifibrotic cytokine.
Patients treated with IFN-γ experienced
improvement of symptoms.
“IFN-γ, through its effect of altering collagen
synthesis, appears to be a key factor to the
treatment of patients with OSMF, & intra-lesional
injections of the cytokine may have a significant
therapeutic effect on OSMF.” (Haque, 2001).
43. IMMUNE MILK
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.
44. TURMERIC
Administration of turmeric powder offers protection
against benzopyrene induced increase in
micronuclei in circulating lymphocytes & it is an
excellent scavenger of free radical in vitro.
Turmeric oil & turmeric oleoresin both act
synergistically in vivo to offer protection against
DNA damage. (Hastak et al., 1997)
45. “Comparative study of the efficacy of curcumin & turmeric
oil as chemopreventive agents in oral submucous
fibrosis: a clinical and histopathological evaluation”
48 cases divided into 3 groups were given curcumin
capsules, turmeric oil & multinal capsules respectively.
Statistically significant improvement was seen clinical signs
& symptoms of cases treated with curcumin & turmeric
oil. Positive changes were also observed in the
histopathological examination of these groups.
Deepa Das A, Anita Balan, Sreelatha KT. JIAOMR. 2010; 22(2): 88-92.
46. OTHER THERAPIES
Injection of Gold, Vitamin A & Collagenase.
Vasodilator injection can be used.
Chemotherapeutic agents like topical bleomycin
can also be used in severe cases.
47. “Pentoxifylline therapy : A new adjunct in the
treatment of oral submucous fibrosis”
14 cases and 15 controls were included in the study.
Test cases were given 400mg pentoxifylline 3 times
daily for 7 months.
Significant improvement was seen in objective criteria
and subjective symptoms.
Rajendran R, Rani V, Shaikh S. Indian J Dent Res 2006;17:1908
48. ORAL PHYSIOTHERAPY
Muscle stretching exercises:
Includes forceful mouth opening with the help of
sticks ballooning of mouth, hot water gargling.
Forceful mouth opening with mouth gag & acrylic
surgical screw.
This is thought to put pressure on fibrous bands.
49. DIATHERMY
Microwave diathermy (Low current is used 20 Watts
x 2450 cycles) is useful in some early or moderately
advanced stages.
Acts by fibrinolysis of bands.
50. ULTRASOUND
It selectively raises the temperature in some well
circumscribed areas.
It is an efficient deep heating modality.
Most of the heat generated by ultrasound is due to
volume heating rather than structural heating.
Ultrasound used for therapeutic purpose has a
frequency of about 0.8-1 MHz and an intensity of
0.5-3 w/cm2.
51. “Physiotherapy for improving mouth opening & tongue
protrusion in patients with Oral Submucous Fibrosis
(OSMF) – Case Series.”
15 cases were treated with Ultrasound therapy, intensity
from 0.7- 1.5 W/cm2 consecutively for 6 days/week for 2
weeks.
The mean improvement in mouth opening was 6.26 mm &
reducing their intensity of burning sensation.
Vijayakumar M, Priya D. Intl J Pharmaceu Sci & Health
Care. 2013: 2(3); 50-57.
52. TREATMENT
Micronutrients and
minerals
TREATMENT DETAILS
Milk from immunized
cows
Vitamin A, B complex, C, D
and E, Fe, Cu, Ca, Zn, Mg, Se
& others
45g milk powder twice a day
for 3 months
Lycopene
8mg twice a day for 2 months
Pentoxyfilline
400mg 3 times a day for 7
months
Intralesional inj (0.01-10U/mL)
3 times a day for 6 months
Submucosal inj twice a week in
multiple sites for 3 months
Interferon gamma
Steroids
Auluck A, Rosin MP, Zhang L, Sumanth KN. Oral submucous fibrosis: a
clinically benign but potentially malignant disease: Report of 3 cases and
review of literature. J Can Dent Assoc 2008; 74; 735-740.
53. TREATMENT
TREATMENT DETAILS
Hyalase +
dexamethasone
Placental extracts
Turmeric
Chymotrypsin,
hyaluronidase and
dexamethasone
Alcoholic extracts of turmeric
(3g), turmeric oil (600 mg),
turmeric oleoresin (600 mg)
daily for 3 months
Chymotrypsin (5000 IU),
hyaluronidase (1500 IU) and
dexamethasone (4 mg), twice
weekly submucosal injections
for 10 weeks
Auluck A, Rosin MP, Zhang L, Sumanth KN. Oral submucous fibrosis: a
clinically benign but potentially malignant disease: Report of 3 cases and
review of literature. J Can Dent Assoc 2008; 74; 735-740.
54. SURGICAL TREATMENT
Simple excision of the fibrous bands.
Split-thickness skin grafting following bilateral temporalis
myotomy or coronoidectomy.
Nasolabial flaps & lingual pedicle flaps.
Surgery to create flaps is performed only in subjects in
whom tongue is not involved.
CO2 –LASER surgery offers advantage in alleviating the
functional restriction.
Cryosurgery- Liquid Nitrogen or Argon gas used preferably
as sprays through „cryoprobe‟ guided by MRI/USG. The
frozen tissue thaws & is either naturally absorbed by the
body or dissolves & forms a scab.
55. “The only way to keep
your health is to eat what you
don’t want, drink what you
don’t like and do what you’d
rather not.”
