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Presented by Dr Niyas Ummer
1st year P G Dept of Oral Medicine and Radiology
Etiopathogenesis and Treatment Strategies of Oral Submucous Fibrosis
Vaibhav Karemore, 2Vaibhav A Karemore
Department of Oral Diagnosis, Medicine and Radiology, VSPM Dental College and Research Centre, Nagpur, Maharashtra, India 2Assistant Professor, Department of Periodontics, Government Dental College and Research Centre, Nagpur, Maharashtra, India Journal of Indian Academy of Oral Medicine and Radiology, October-December 2011;23(4):598-602
• Oral Submucous Fibrosis (OSMF)
– Chronic debilitating disease, and a premalignant condition – Associated with betel nut and gutkha chewing
– – – – Generalized submucosal fibrosis Reduction in vasculature Atrophy of surface epithelium Dysphagia (severe cases)
• 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
1954) • Idiopathic palatal fibrosis (Rao. 1962) . 1952) • Idiopathic scleroderma of mouth (Su.Synonyms • Atrophia idiopathica (tropica) mucosae oris (Schwartz. 1962) • Sclerosing stomatitis (Behl.
Merchant AT. Fikree FF. Rahbar MH (1999) .Classification Systems • Pindborg JJ (1989) • Khanna JN and Andrade NN (1995) • Haider SM.
Pindborg’s Classification • Based on clinical features – Stage 1 (Stomatitis) – Stage 2 (Fibrosis in healing vesicles and ulcers) – Stage 3 (Sequelae) .
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 .
Rahbar MH • Staging the disease clinically and functionally depending on the location of bands as well as the maximum mouth opening: – A. Merchant AT.Haider SM. Functional staging: . Fikree FF. Clinical staging: – B.
brownish red discoloration of mucosa with irregular surface which tends to desquamate .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 .
Hematological Abnormalities • • • • • • Increased erythrocyte sedimentation rate Iron-deficiency anemia Decrease in serum iron Increase in total iron binding capacity (TIBC) Eosinophilia Increased gamma globulin .
Greek aitiologia ("giving a reason for”) ETIOLOGY .
Etiological Factors • • • • • Arecanut chewing Ingestion of chillies Genetic processes Immunologic process Nutritional deficiencies .
the most abundant alkaloid.upregulate lysyl oxidase activity . might have cytotoxic effects on cells and is also demonstrated to promote collagen synthesis .Arecanut Chewing • High copper content .result in fibrosis • Arecoline.
observed oral submucous fibrosis like response in wistar rats on application of capsaicin (active principle of chillies) • Hamner et al failed to support chillies as one of the cause for OSMF. • Supported by Sirsat and Khanolkar .Ingestion of Chillies • Common in Indians • Considered as a source of allergen for OSMF in a study by Pindborg and Singh. in a study carried out in hamster cheek pouch .
B7 and DR3 were found in OSMF patients when compared to normal individuals .that genetic factor allele A6 confers risk of developing disease • Liu et al .Genetic Processes • Studies indicate .increased risk associated with cytotoxic T lymphocyte associated antigen 4 + 49 G allele • Raised values of human leukocyte antigen (HLA) A10.
observed in patients with oral leukoplakia and OSMF .Immunologic Process • Reduced natural killer cell activity .
Nutritional Deficiencies • Higher frequencies of deficiencies of vitamin A. B. C and multiple vitamin deficiencies indicated to be of etiologic importance .
genesis ("creation") PATHOGENESIS .Greek pathos ("disease").
hormones. including growth factors.take place through collagen production pathway and collagen degradation pathway • In the initial events of disease .arecanut acts as a major initiative agent .• Rajalalitha P and Vali – collagen forms a major component in OSMF – collagen disorder • Synthesis of collagen is influenced by variety of mediators. cytokines and lymphokines • Molecular events .
• 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 .
Prabhu. Dinesh V. Vidya M Increased serum copper levels could cause an upregulation of the enzyme lysyl oxidase leading to cross-linking of collagen and elastin .• Luquman M.
treating anemia.resulted in initial improvement .relief in signs and symptoms along with increase in mouth opening (temporary) • Conservative treatment (stopping the consumption of chillies and other irritants.led to more severe fibrosis (modern grafting techniques have improved prognosis) • Medical treatment (submucosal steroidal injection) .Paissat DK (1981) • Surgical treatment . and encouraging a balanced diet with vitamin B supplements and regular review) .
gave satisfactory and successful result . – Corticosteroids – Surgical cutting of fibrotic bands • Results: – Surgical resection of bands done with split thickness skin graft. along with stoppage of habit . gold or vitamin A. E – Injection of senotyphoid and iodides internally.Yen DJC (1982) • Compared: – Local injection of fibrinolytic agent.
balanced diet and stretching 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 .Hayes PA (1985) • Conservative mode of treatment (stoppage of habit. vitamins supplements.
oral mucosa is susceptible to chronic inflammatory changes if they chew betel nut • Medical management (injections of hyaluronidase. hydrocortisone.Caniff JP.improve mouth opening in mild cases • Surgical therapy – the only effective treatment for severe cases . Harvey W. Harris M (1986) • OSMF has multifactorial etiology • Patients with genetic predisposition . placental extract. vitamin and iron supplements) of the disease has been both empirical and unsatisfactory • Intralesional steroid . triamcinolone.
early and significant relief of symptoms – but recurrence of fibrotic bands – Response to placental extract was poorest .Gupta Deepak. Sharma SC (1988) • Compared – injection dexamethasone in combination with chymotrypsin and hyaluronidase – placental extract and placental graft • Results: – Good results in group one – Treated with submucosal placental graft .
Borle RM. feeling of stiffness and vesicles disappeared.burning sensation. but no improvement in mouth opening – Trismus was more pronounced in group one patients in followup 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” . Borle SR (1991) • Compared submucosal injection of triamcinolone and chewable tablets of vitamin A with ferrous fumarate and topical betamethasone drops • Results: – In both .
arrested or even reversed the progress of premalignant cells to cells with invasive malignant potential • Cellular concentration of amino acids. Singh SP. enzymes and vitamins help in regeneration of tissues .55% • Vitamin A – major role in induction and control of epithelial differentiation in mucous secretary and keratinization tissues .Katharia SK.it delayed. slowed. 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.
Chen HR. Lin LM. topial and submucosal injection of steroid) – Surgical therapy (surgical flaps) • Results: – Medical treatment (vitamins and steroid injections) gave symptomatic relief in mild cases – Surgical treatment showed significant improvement in interincisal opening in severe cases (but with varying amount of wound contraction) . Tsai CC (1995) • Treated 150 patients of OSMF over 10 years • By either – Medical therapy (vitamin B complex. Huang YL. vasodilator.Lai DR.
Khanna JN. • Disease in early stage .local injection of triamcinolone acetonide • Result: – Improvement in the clinical picture and mouth opening • Advanced cases . Andrade NN (1995) • 100 cases .2 groups as early and advanced cases.surgical intervention • Result: – Improved mouth opening (increase of 20 to 31 mm) – Regression of other clinical symptoms .
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 .
Aga Perin. Jhonson Newell W.Meher Rehana. and minerals 117 patients • Result: – Improvement in symptoms and signs in patients with micronutrient deficiency – however. vitamin B. vitamin C. vitamin D. Rengaswamy S and Saman W (1997) • Combination of micronutrients like retinol. interincisal distance was not significantly improved at exit .
effect on collagen synthesis by arecoline stimulated OSMF fibroblast • IFN injections given • Result: – Inhibition of collagen synthesis – Significant improvement in mouth opening .Haque MF et al (2001) • Interferon (IFN) gamma .antifibrotic cytokine .
Tai YS.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) . Liu BY et al (2001) • Oral administration of immunized cow milk twice daily for 3 months • Mechanism of action: An anti inflammatory component .
B and C • Observation: Lycopene can and should be used as a first line of therapy in the initial management .increase of 3.16 mg of lycopene – Group B .given a placebo • Mouth opening values .4.Kumar A et al (2007) • Efficacy of oral lycopene therapy • 58 patients with OSMF . 4.divided into 3 groups • Evaluated weekly over a 2-month period – Group A .0 mm for groups A.16 mg of lycopene + biweekly intralesional steroid injections – Group C .6 and 0.
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 with injection of placental extract intralesionally associated with antioxidants and jaw dilator exercises has been found useful in 52 cases” .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) .
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 be taken every day – Advanced cases of trismus are treated by jaw dilation under general anesthesia with incision of fibrous bands .• They recommended the treatment protocol to be given as follows: – Local injection of placental extract 2 ml (market preparation manufactured from 0.
it can be said that there is hope for further detail evaluation of etiopathogenesis as well as management of this disorder for having better life to these patients suffering from this precancerous condition .CONCLUSION • As long span of time has been passed since first diagnosis of OSMF and treatment given for it till this era. • Reasons may be the unpredictable etiology. no complete success has been achieved. immune response or immune status of individual patient. and pros and cons of every treatment modality depending on the stage of the OSMF • After having a glance on vast literature on OSMF.
Critical Evaluation • Strengths: – Comprehensive overview of OSMF – Various modalities of treatment have been described and discussed – 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 tobacco used .
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