COMPREHENSIVE INSIGHT INTO MANAGEMENT OF OSMF

Christopher Vinay Shinde 1 and Sahil Kohli 2 . 1. Senior Lecturer, Department of Oral Medicine and Radiology, Mansarovar Dental College Hospital and Research Centre, Bhopal, MP, India. 2. Senior Lecturer, Department of Oral Medicine and Radiology, RKDF Dental College and Research Centre, Bhopal, MP, India. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


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and calcium sodium phosphosilicate. Sodium monofluorophosphate, sodium fluoride, sodium fluoride/stannous fluoride combinations. 46 Oral prophylaxis in form of scaling supplemented by use of mouthwash and gum paints containing astringents like tannic acid, antiseptics like chlorhexidine or iodine and analgesics like choline salicylate.
These measures thus aim at achieving complete oral health and building a positive self esteem in the patients.

Symptomatic Treatment:-
Symptomatic treatment aims at relieving the symptoms caused due to OSMF like xerostomia, burning sensation in mouth, dysguesia and oral ulcers. Vesiculation accompanied by ulcers, traumatic ulcers and pain in the oral cavity are common in OSMF patients. These include chewing of sugar-free chewing gums to keep mouth moist. Topical anesthetic agents in form of mouth paints or mouthwashes. Systemic analgesics like diclofenac sodium, ibuprofen, paracetamol may be given in case of severe pain.

4.Treatment per se:-Medical treatment: topical and systemic(table-1):-Surgical treatment:-
Medical Treatment:-Topical medications are prescribed in almost all stages of OSMF. These agents provide localized action without systemic adverse effects. These may be associated with bad taste and smell, nausea, dry mouth, candidiasis, mucosal atrophy, delayed healing, allergy/contact dermatitis to medication itself, preservatives, other ingredients in vehicles. Systemic medications are usually reserved for severe and refractory cases as these medications are associated with many adverse effects when compared to topical medications. Saravana KB et al in their review discussed the treatment protocol depends on the grading of the disease as follows: Grade I:-Antioxidants and multivitamins 1 tab once daily 10 weeks orally, iron supplements 1 tab once daily 10 weeks orally, ointment triamcinolone acetonide 0.10% 4 weeks topically.
Grade IV:-Antioxidants and multivitamins 1 tab once daily 10 weeks orally, iron supplements 1 tab once daily 10 weeks orally, Inj. Placentrex 2 ml weekly once for 4 weeks intralesionally, ointment triamcinolone acetonide 0.10% 4 weeks topically, local injection of corticosteroids and placental extracts have been tried in addition to hyaluronidase, collagenase and similar substance that breakdown intercellular substances and reduces collagen formation. Intralesional injection of hyaluronidase mixed with hydrocortisone resulted in better results. Intralesional injections of IFN-gamma which is also known as antifibrotic cytokine is another key factor to the treatment of OSMF. IFNgamma can alter collagen synthesis. Local and systemic application of glucocorticoids and placental extracts are commonly used which prevents mucosal damage because of its anti inflammatory effects.

Placental extracts
3. Combination regimen 4. Turmeric 5.Aloe vera 6. Interferon gamma 7. Oral mucoadhesive drug delivery TOPICAL:-1.Corticosteroids:-Steroids are most commonly used in the management of OSMF because of their anti-inflammatory properties. Cytokines and growth factors produced by the inflammatory cells can promote the fibrosis by inducing a proliferation of fibroblast, subregulating collagen synthesis and down regulation collagenase production. Steroids exert their anti-inflammatory action by inhibiting the apoptosis of inflammatory cells. 19 Short acting drugs: Hydrocortisone intralesional injection 1.5cc given once a week for a duration of 12 weeks have proven to be beneficial. Systemic corticosteroids were found to be useful in only early and mild cases.
Intermediate acting drugs: Topical triamcinolone acetonide 0.1% and local injection of triamcinolone acetonide can be used in very early and early cases.
Long acting drugs: Dexamethasone 4mg intralesional injections, is given biweekly. It can be given in combination with hyaluronidase for better long term results. Betamethasone can be given as 4mg/ml intralesional injections biweekly. Usage:-Chymotrypsin (5000 IU), twice weekly submucosal injections for 10 weeks. 53 Hyaluronidase:-It breaks down hyaluronic acid (ground substance of connective tissue), lowers the viscosity of intracellular cement substance i.e hyaluronidase decreases cell formation by virtue of its action on hyaluronic acid, which plays an important role in collagen formation. The use of topical hyaluronidase has been shown to improve symptoms more quickly than steroids alone. The combination of steroids and topical hyaluronidase shows better long-term results than either agent used alone. 22,52 Usage:-Hyaluronidase (1500 IU) twice weekly submucosal injections for 10 weeks.

Collagenase:-
It is a lysosomal enzyme, capable of degrading phosphate esters, proteins, polysaccharides, glycosides and sulphate esters. Reduced content of functional collagenase observed in OSMF patients is one of the mechanisms accountable for collagen accumulation. Lin and Lin found that intra-lesional collagenase injections not only results in a noteworthy improvement of mouth opening, but also experience a striking decline in symptoms.
Usage: 2mg of collagenase materials dissolved in 1ml of distilled water for injection. 54 Adverse reactions: pain, swelling and trismus may be seen after injections of collagenase which is considered to be allergic reaction of this agent. 42

Placental Extracts:-
Placental extract is an aqueous extract of human placenta that contains nucleotides, enzymes, vitamins, amino acids, and steroids. Its action is essentially "biogenic stimulation." It is suggested that it stimulates the pituitary and the adrenal cortex, and regulates the metabolism of tissues. Its use is based on the tissue therapy method. According to this theory when animal and vegetable tissues are severed from the parent body and exposed to unfavourable conditions, but not mortal to their existence, undergo biogenic readjustment leading to development of substance in the state of their survival to ensure their vitality biogenic stimulators. Such tissues or their extract when implanted or injected into the body after resistance of pathogenic factors stimulates metabolic or regenerative process thereby favouring recovery. The intra-lesional injection of human placental extract had been shown to be effective, lasting, and safe. There was significant improvement in mouth opening and associated symptoms. 19,10 Usage:lnjection of Placenta extract (lnj. PLACENTREX) 2 ml was given locally in the predetermined areas, once a week for total duration of one month or more.

4.Turmeric:-
Turmeric has been found to inhibit many disease processes through their anti-inflammatory, antioxidant and anticancer properties. In addition, Curcuminoids isolated from turmeric, has been found to have effective 418 antioxidant, DNA-protectant and antimutagen action. 6 Turmeric oil & turmeric oleoresin both act synergistically in vivo to offer protection against DNA damage. 19,6 Usage:-Topical application of alcoholic extracts of turmeric (3 g), turmeric oil (600 mg), turmeric oleoresin (600 mg) daily for 3 months. 55 5. Aloe Vera:-Aloe vera foliage, extract and resin present antimicrobial, anti-inflammatory and healing properties. It is easily available, safe to use, cost effective, non-invasive and effective treatment modality for OSMF. Thus it can be an adjuvant therapy in treatment of OSMF. 21 Usage:-Aloe vera can be applied topically (approx. 5mg 2-3 times a day) and/or systemic (30 ml juice twice daily).

6.Interferon Gamma:-
It plays an important role in the treatment of patients with OSMF because of its immuno-regulatory effect. IFNgamma is a known anti-fibrotic cytokine. Patients treated with an intra-lesional injection of IFN-gamma experienced improvement of symptoms. IFN gamma, through its effect of altering collagen synthesis, appears to be a key factor to the treatment of patients with OSMF, and intralesional injections of the cytokine may have a significant therapeutic effect on OSMF. 19,16 Usage:-Intralesional injection of interferon gamma (0.01-10.0 U/mL) 3 times a day for 6 months.

7.Oral Mucoadhesive Drug Delivery:-
Oral mucoadhesive drug delivery is very efficient therapeutic targeted drug approach than systemic delivery, as smaller amounts of drug can be easily dispersed at the site of the disease, thereby reducing its side effects. Mucoadhesive systems for oral local drug delivery include adhesive tablets, adhesive patches, adhesive films or pellicles, adhesive semisolid systems (gels, ointments), and adhesive liquid systems (sprays, mouthwashes). Kumar  Pentoxyfylline is a tri-substituted methylxanthine derivative, which increases red cell deformability, leukocyte chemotaxis, antithrombin and anti-plasmin activities, and more importantly to the present context, its fibrinolytic activity. Pentoxifylline decreases red cell and platelet aggregation, granulocyte adhesion, fibrinogen levels, and whole blood viscosity. 13,17 Usage: 400-800 mg twice/thrice daily.
Nylidrin hydrochloride a peripheral vasodilator affects the tissues in diffuse fibrosis to a noticeable degree by relieving the local ischemic effect and also helps the nutritional and therapeutic substances to reach the affected tissues. 42 Usage: 3 to 12 mg 3-4 times a day.
Buflomedial hydrochloride a vasoactive agent, acts on the microcirculation, relieves the ischemic effect and thus helps the nutritional and therapeutic substances reach the affected tissues. It can be used as effective adjunct drug both in early and advanced cases of OSMF Usage: 450mg/day 42 419 2.Immunomodulators:-Immunomodulators act by opposing the action of soluble factors released by sensitized lymphocytes following activation by specific antigens or by immunosuppressive action. These agents also prevent or suppress inflammatory reactions. 57 Levamisole is an antihelminthic immunomodulator drug which modifies both cellular and humoral immunity. Levamisole may be given alone/combined with other modalities. Usage: Levamisole 50 mg, three times daily, for three consecutive days in a week for three alternate weeks.
Immune milk: It is a kind of skimmed milk produced from cows immunized with multiple human intestinal bacteria. It has good anti-inflammatory effect and contains moderate amounts of Vit. A, C, B1, B2, B6, B12, nicotinic acid, pantothenic acid, folic acid, iron, copper and zinc and it contains 20-30% higher concentration of IgG type I antibody. It may suppress the inflammatory reaction and modulate cytokine production. 19 Usage: 45 g milk powder twice a day for 3 months. 58

Fibrotomy:-
The surgical treatment involves excision of fibrous bands and forceful mouth opening resulting in a raw wound surface. Relapse is a common complication that occurs after surgical release of the oral trismus caused by OSMF. 27 Fibrotomy with grafts:-Initially surgeons aimed at surgical elimination of the fibrotic bands which showed further scar formation and recurrence of trismus, to prevent which, they started using various inter positional graft materials. The principle behind is incision (incorrectly termed as excision) or surgical release of fibrous bands followed by forceful opening of the mouth (widening of the incised tissue or region), and covering of surgical defects using various flaps or synthetic biological material.  Lycopene:-Lycopene is a bright red carotene and carotenoid pigment and phytochemical found in tomatoes and other red fruits and vegetables. It has been shown to have several potent anti-carcinogenic and antioxidant properties. Lycopene exhibits the highest physical quenching rate constant with singlet oxygen. The role of lycopene in OSMF is inhibition of abnormal fibroblast, increase resistance to stress, decrease in inflammatory response. It has found to improve mouth opening and reduces burning sensationsingly or in combination of intralesional steroids. 22,63 Usage: 8 mg twice a day for 2 months.

Alpha-Lipoic Acid:-
It has a good potential action of scavenging free radicals and also it has excellent property, it can dissolve in both water and fat. It has shown reduction in burning sensation and improved mouth opening. Kneading is an effective form of massage therapy in form of gentle soft tissue manipulation helps in improving the elasticity of fibrous tissues and mobilizing scar tissues.
Muscle stretching exercises can be performed using mouth gag, acrylic surgical stent, ballooning of mouth, hot water gargling, inter positioning spatula between the teeth and adding a new spatula every 5-10 days. 6 Heat -Short wave/Micro wave diathermy: Heat has been used in the form of lukewarm water, hot rinses or selective deep heating therapies like short wave or micro wave diathermy. Microwave diathermy seems superior to short wave, because selective heating of juxta epithelial connective tissue, thereby limiting the area treated. Ultrasound is a form of acoustic vibration with frequencies so high that it can't be perceived by human ear. Ultrasound used for therapeutic purpose has a frequency of about 0.8-1 MHz and an intensity of 0.5-3 w/cm 2 . Ultrasound selectively raises the temperature in some well circumscribed areas. Ultrasound thus proves to be an efficient deep heating modality. 59 422 c.Rehabilitation:-Rehabilitation includes post surgical rehabilitation, oral physiotherapy and also prosthodontic rehabilitation wherever required after endodontic treatment that is placement of crown and bridge also crown for severly attrited teeth. This is important step in restoration of proper form and function for esthetic and functional harmony.

Conclusion:-
OSMF is one of the most poorly understood and unsatisfactorily treated diseases. Despite elaborate researches on the etiology, pathogenesis and management protocol of the disease, there has been no universally accepted cure reported in the scientific literature. All available treatments provide symptomatic relief, which is short lived. This is mainly due to the fact that the etiology of the disease is not fully understood and the disease is progressive in nature. Based upon above mentioned treatment modalities and our experience we can conclude that management of OSMF depends on the degree of clinical involvement (table-2). If the disease is detected at a very early stage, cessation of the habit is sufficient. Most patients with OSMF present with moderate-to-severe disease which is irreversible. A combined therapy with holistic approach can help our patient care though it still is the field requiring extensive research.