etiopathogenesis & treatment of osmf
TRANSCRIPT
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Etiopathogenesis
and
Treatment Strategies of
Oral Submucous Fibrosis
Presented by
Dr Niyas Ummer
1styear P G
Dept of Oral Medicine and Radiology
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Etiopathogenesis and TreatmentStrategies of Oral Submucous
Fibrosis
1Tapasya Vaibhav Karemore, 2Vaibhav A Karemore1Reader, Department of Oral Diagnosis, Medicine and Radiology, VSPM Dental
College and Research Centre, Nagpur, Maharashtra, India2Assistant Professor, Department of Periodontics, Government Dental College and
Research Centre, Nagpur, Maharashtra, India
Journal of Indian Academy of Oral Medicine and Radiology, October-December2011;23(4):598-602
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Introduction
Oral Submucous Fibrosis (OSMF)
Chronic debilitating disease, and a premalignantcondition
Associated with betel nut and gutkhachewing
Characteristics:
Generalized submucosal fibrosis
Reduction in vasculature
Atrophy of surface epithelium
Dysphagia (severe cases)
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Prevalence
5 million affected in Indian subcontinent
7.6 % malignant transformation rate
0.2 to 2.3 % in males
1.2 to 4.57 % in females
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Synonyms
Atrophia idiopathica (tropica) mucosae oris(Schwartz, 1952)
Idiopathic scleroderma of mouth (Su, 1954)
Idiopathic palatal fibrosis (Rao, 1962)
Sclerosing stomatitis (Behl, 1962)
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Classification Systems
Pindborg JJ (1989)
Khanna JN and Andrade NN (1995)
Haider SM, Merchant AT, Fikree FF, Rahbar MH(1999)
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PindborgsClassification
Based on clinical features
Stage 1 (Stomatitis)
Stage 2 (Fibrosis in healing vesicles and ulcers)
Stage 3 (Sequelae)
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Khanna JN and Andrade NN
Classification system for the surgical
management of OSMF:
Group I: Very early cases
Group II: Early cases
Group III: Moderately advanced cases
Group IVA: Advanced cases
Group IVB: Advanced cases with premalignant and
malignant changes
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Haider SM, Merchant AT, Fikree FF,
Rahbar MH
Staging the disease clinically and functionally
depending on the location of bands as well as
the maximum mouth opening:
A. Clinical staging:
B. Functional staging:
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Symptoms
Most common initial symptoms: Burning sensation
Ulceration and recurrent stomatitis
Intraoral petechiae
Defective gustatory sensation Dryness of mouth and/or hypersalivation
Pain in the ear or decrease in hearing ability
Pigmentation In betel quid chewers - brownish red discoloration of
mucosa with irregular surface which tends todesquamate
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Hematological Abnormalities
Increased erythrocyte sedimentation rate
Iron-deficiency anemia
Decrease in serum iron Increase in total iron binding capacity (TIBC)
Eosinophilia
Increased gamma globulin
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ETIOLOGY
Greek aitiologia ("giving a reason for)
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Etiological Factors
Arecanut chewing
Ingestion of chillies
Genetic processes Immunologic process
Nutritional deficiencies
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Arecanut Chewing
High copper content - upregulate lysyl oxidase
activity - result in fibrosis
Arecoline, the most abundant alkaloid, might
have cytotoxic effectson cells and is also
demonstrated topromote collagen synthesis
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Ingestion of Chillies
Common in Indians
Considered as a source of allergenfor OSMF in a studyby Pindborg and Singh.
Supported by Sirsat and Khanolkar - observed oralsubmucous fibrosis like response in wistar rats on
application of capsaicin(active principle of chillies)
Hamner et alfailed to support chillies as one of thecause for OSMF, in a study carried out in hamster cheekpouch
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Genetic Processes
Studies indicate - that genetic factor allele A6
confers risk of developing disease
Liu et al- increased risk associated with cytotoxic
T lymphocyte associated antigen 4 + 49 G allele
Raised values of human leukocyte antigen (HLA)A10, B7 and DR3 were found in OSMF patients
when compared to normal individuals
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Immunologic Process
Reduced natural killer cell activity - observed
in patients with oral leukoplakia and OSMF
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Nutritional Deficiencies
Higher frequencies of deficiencies of vitamin
A, B, C andmultiple vitamin deficiencies -
indicated to be of etiologic importance
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PATHOGENESIS
Greek pathos ("disease"), genesis ("creation")
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Rajalalitha P and Valicollagen forms a major
component in OSMFcollagen disorder
Synthesis of collagen is influenced by variety of
mediators, including growth factors, hormones,
cytokines and lymphokines
Molecular events - take place through collagen
production pathwayand collagen degradation
pathway
In the initial events of disease - arecanut acts as a
major initiative agent
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Transforming growth factor beta (TGF-beta) -
role in wound repair and fibrosis - causes
deposition of extracellular matrix by increasing
the synthesis of matrix proteins like collagen and
decreasing its degradation by stimulating various
inhibitory mechanisms
Action on genes is mostly exerted at the
transcription level through ill-defined intracellular
pathway
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Luquman M, Dinesh V, Prabhu, Vidya M -
Increased serum copper levels could cause an
upregulation of the enzyme lysyl oxidase -
leading to cross-linking of collagen and elastin
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MANAGEMENT
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Paissat DK (1981)
Surgical treatment- resulted in initial improvement- led to
more severe fibrosis (modern grafting techniques have
improved prognosis)
Medical treatment(submucosal steroidal injection) - relief
in signs and symptoms along with increase in mouth
opening (temporary)
Conservative treatment (stopping the consumption of
chillies and other irritants, treating anemia, and
encouraging a balanced diet with vitamin B supplements
and regular review)
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Yen DJC (1982)
Compared:
Local injection of fibrinolytic agent, gold or vitamin A, E
Injection of senotyphoid and iodides internally,
Corticosteroids
Surgical cuttingof fibrotic bands
Results: Surgical resection of bands done with split thickness skin
graft, along with stoppage of habit - gave satisfactory and
successful result
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Hayes PA (1985)
Conservative mode of treatment (stoppage ofhabit, vitamins supplements, balanced diet andstretching exercises)
Results:
Increased maximum mouth opening (3 mm)
Decreased blanching of oral mucosa
Increased buccal mucosal resiliency
No recurrence of vesicles
Less tenderness to palpation
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Caniff JP, Harvey W, Harris M (1986)
OSMF has multifactorial etiology
Patients with genetic predisposition - oral mucosa is
susceptible to chronic inflammatory changes if they chew
betel nut
Medical management(injections of hyaluronidase,
hydrocortisone, placental extract, triamcinolone, vitamin
and iron supplements) of the disease has been both
empirical and unsatisfactory
Intralesional steroid - improve mouth opening in mild cases
Surgical therapythe only effective treatmentfor severe
cases
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Gupta Deepak, Sharma SC (1988)
Compared
injection dexamethasonein combination with chymotrypsin
and hyaluronidase
placental extract and placental graft
Results:
Good results in group one
Treated with submucosal placental graft - early and significant
relief of symptomsbut recurrence of fibrotic bands
Response to placental extract was poorest
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Borle RM, Borle SR (1991)
Compared submucosal injection of triamcinolone and
chewable tablets of vitamin A with ferrous fumarate and
topical betamethasone drops
Results:
In both - burning sensation, feeling of stiffness and vesicles
disappeared, but no improvement in mouth opening
Trismus was more pronounced in group one patients in follow-
up period
All surgical treatments tried so far are useful in advanced
cases whereas conservative treatments are better option at
earlier stage of OSMF with proper habit restriction
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Katharia SK, Singh SP, Kulshreshtha VK
(1992)
Injecting placental extract locally in the predetermined areas once
a week for 1 month
Result:
Highly significant improvement in the mouth opening of about 28.26%
Color of the oral mucosa improved up to 38.55%
Vitamin Amajor role in induction and control of epithelial
differentiationin mucous secretary and keratinization tissues - it
delayed, slowed, arrested or even reversed the progressof
premalignant cells to cells with invasive malignant potential
Cellular concentration of amino acids, enzymes and vitamins help in
regeneration of tissues
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Lai DR, Chen HR, Lin LM, Huang YL, Tsai
CC (1995)
Treated 150 patients of OSMF over 10 years
By either
Medical therapy (vitamin B complex, vasodilator, topial and
submucosal injection of steroid) Surgical therapy (surgical flaps)
Results:
Medical treatment (vitamins and steroid injections) gavesymptomatic relief in mild cases
Surgical treatment showed significant improvement in
interincisal opening in severe cases (but with varying amount of
wound contraction)
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Khanna JN, Andrade NN (1995)
100 cases - 2 groups as early and advanced cases.
Disease in early stage - local injection of triamcinoloneacetonide
Result:
Improvement in the clinical picture and mouth opening
Advanced cases - surgical intervention
Result: Improved mouth opening (increase of 20 to 31 mm)
Regression of other clinical symptoms
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Yeh CY (1996)
Performed incision of fibrotic bands
Buccal defect was covered by a pedicle buccal fat
pad
Postop mouth exercises
Result:
Satisfactory improvement in mouth opening
M h R h A P i Jh
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Meher Rehana, Aga Perin, Jhonson
Newell W,
Rengaswamy S and Saman W (1997) Combination of micronutrientslike retinol,
vitamin B, vitamin D, vitamin C, and minerals -
117 patients
Result:
Improvement in symptoms and signsin patients withmicronutrient deficiency
however, interincisal distance was not significantly
improvedat exit
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Haque MF et al (2001)
Interferon (IFN) gamma- antifibrotic cytokine
- effect on collagen synthesis by arecoline
stimulated OSMF fibroblast
IFN injections given
Result:
Inhibition of collagen synthesis
Significant improvement in mouth opening
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Tai YS, Liu BY et al (2001)
Oral administration of immunized cow milktwice daily for
3 months
Mechanism of action:
An anti inflammatory component - may suppress the
inflammatory reaction and modulate cytokine production
Results:
Improvement of signs and symptoms in 20 to 80% 70% showed significant increase in maximum mouth opening (3
mm)
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Kumar Aet al (2007)
Efficacy of oral lycopene therapy
58 patients with OSMF - divided into 3 groups
Evaluated weekly over a 2-month period
Group A - 16 mg of lycopene
Group B - 16 mg of lycopene + biweekly intralesional steroid injections
Group C - given a placebo
Mouth opening values - increase of 3.4, 4.6 and 0.0 mm for groups
A, B and C
Observation:
Lycopene can and should be used as a first line of therapyin the
initial management
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Sharma VK et al (2009)
Injected placental extract intralesionally in the soft palate and in
the fibrous bands formed anterior to anterior pillars (at multiple
sites bilaterally) - given every week for 10 weeks
Stoppage of habit
Results (followed for total duration of 6 months):
Excellent results
Simple office procedure in cases of oral submucous fibrosis withinjection of placental extract intralesionally associated with
antioxidants and jaw dilator exercises has been found useful in 52
cases
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They recommended the treatment protocol to be given
as follows:
Local injection of placental extract2 ml (market
preparation manufactured from 0.1 gm of fresh human
placenta) given at multiple sites at soft palate and anterior
to anterior pillars (as shown in the figure with red marking)
every week for 10 weeks Lycopene(10%) 2000 mcg orally
Methylcobalmin injection (1500 mcg) given
intramuscularly every week
Jaw dilators exercises explained to the patients to betaken every day
Advanced cases of trismus are treated byjaw dilation
under general anesthesia with incision of fibrous bands
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CONCLUSION
As long span of time has been passed since first diagnosis of OSMF
and treatment given for it till this era, no complete successhas been
achieved.
Reasons may be the unpredictable etiology, immune response orimmune status of individual patient, andpros and cons of every
treatment modalitydepending on the stage of the OSMF
After having a glance on vast literature on OSMF, it can be said thatthere is hope forfurther detail evaluation of etiopathogenesis as
well as management of this disorder for having better life to these
patients suffering from this precancerous condition
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Critical Evaluation
Strengths: Comprehensive overview of OSMF
Various modalities of treatment have been described anddiscussed
Good systems of classification given
Weaknesses: No detailed etiologies
Pathogenesis lacks molecular aspect No details about collagen fiber orientation
No description or comparison of various forms of tobaccoused
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