Etiopathogenesis & Treatment of OSMF

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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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Etiopathogenesis & Treatment of OSMF

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