Oral submucous fibrosis is a well-recognized potentially premalignant lesion of the oral cavity. Oral submucous fibrosis is also a common disease in countries where betel nuts are chewed habitually. It is believed to have multiple causes. Local irritants (betel nuts, tobacco, and spicy food), general nutrition, and vitamin deficiencies are considered to risk factors for oral submucous fibrosis [5
Clinically, the earliest sign of oral submucous fibrosis is mouth soreness with constant burning upon eating spicy foods. Oral submucous fibrosis is clinically divided into 3 stages: stomatitis, fibrosis, and sequelae [6
]. During the stomatitis phase, the oral mucosa contains areas of erythema in which vesicles appear. These vesicles later rupture producing ulcers that heal via fibrosis. The primary presenting complaint in this disease is progressive trismus from fibrosis of the buccal submucosa.
Treatment is based on severity of disease. Typically, if the disease is noted before development of trismus, cessation of the betel habit will often resolve the disease. Once trismus has developed and disease is now considered mild to moderate, oral submucous fibrosis is irreversible disease, with the goal of medical and surgical therapy to maintain oral function and limit progression of disease. Treatment at this stage is focused on restoring mandibular range of motion, oral cancer surveillance, and cessation of betel nut habit. Physical therapy combined with medical treatment is often utilized. Medical therapy in the United States is limited to weekly submucosal injections of steroids to limit progression of oral submucous fibrosis [7
]. For cases in which initial surgical intervention is unsuccessful resulting in recurrent trismus usually secondary to lack of compliance with physical therapy or less commonly from shrinkage of the skin graft or alloplastic graft a more aggressive surgical therapy is indicated. Again, through excision of any fibrous bands intraorally, repeated masticatory muscle myotomy is required. Often in this situation, a larger soft tissue buccal defect is created needing large soft tissue reconstruction. This can include a temporalis pedicled flap, superficial temporalis fascia pedicled flap, or a radial forearm free flap combined with split thickness skin graft coverage [8
Steroids and especially glucocorticoids were first used in the treatment of oral submucous fibrosis and were extensively used in the past several decades because of their anti-inflammatory property. Cytokines and growth factors produced by inflammatory cells can promote fibrosis by inducing a proliferation of fibroblasts, upregulating collagen synthesis and downregulating collagenase production. Several glucocorticoids were used such as short-acting drugs (hydrocortisone), intermediate-acting drugs (triamcinolone), and long-acting drugs (betamethasone and dexamethasone). Glucocorticoids exert their anti-inflammatory activity by inhibiting the generation of inflammatory factors and increasing the apoptosis of inflammatory cells. They partially relieved patients of their symptoms at an early stage of oral submucous fibrosis as confirmed in many studies [10
]. Steroids were less useful in reversing he abnormal deposition of fibrotic tissues and thus this treatment was always associated with a high incidence of relapse.
Several emerging advances were made past few years for the management of oral submucous fibrosis with promising results. Further studies recognized that proliferative fibroblasts, inactive collagenase, and the inhibited fibrinolytic system contributed to the initiation and development of oral submucous fibrosis [12
]. In a controlled clinical trial, H. J. Lin and J. C. Lin found that intralesional injections of collagenase resulted not only in significant improvement in mouth-opening but also in a striking reduction of hypersensitivity to spices, sour, cold, and heat. These results indicated that collagenase treatment was approximately fivefold more effective than triamcinolone diacetate [14
]. Hyaluronidase also showed a much quicker effect in ameliorating the burning sensation and painful ulceration than did dexamethasone, though the effect was short-term [15
]. Chymotrypsin, an endopeptidase, hydrolyzes ester and peptide bonds. It was also used as a proteolytic and anti-inflammatory agent in the treatment of oral submucous fibrosis [16
Yen was the first to succeed in coveting the buccal defect with a split-thickness skin graft in treating a case of oral submucous fibrosis [17
]. Kavarana and Bhathena filled the defect after sectioning of fibrous bands with 2 inferiorly based nasolabial flaps and division of the pedicle after 3 weeks they observed average mouth opening of 2.5
cm with acceptable external scars [18
]. R. M. Borle and S. R. Borle reported disappointing results with skin grafting to cover the raw area and used tongue flap to cover the defect [19
]. Khanna and Andrade reported the incidence of shrinkage, contraction, and rejection of split skin graft as very high leading to poor oral condition with recurrence in 12 cases [20
]. Mehrotra et al. present a case series of 100 patients where they compared buccal fat pad graft, tongue flap, nasolabial fold flap, and split skin graft for correction of mucosal defect created after incising the fibrous bands. Esthetics and function achieved with split skin graft were good but showed some degree of relapse due to contracture of the graft. They found that buccal fat pad rotation was superior to other procedures [21
Microscopically diffuse fibrosis in the submucosa with a chronic inflammatory infiltrate is the hallmark of oral submucous fibrosis. Atrophic changes in the mucosal layer include thinning of the epithelium, loss of rete ridges, sawtoothing, and liquefaction degeneration of the basal layer. Pigmentation is incontinence; Isaac et al. found that pigmentation was present in 62% of the 35 specimens they studied [22
]. Areas of ulceration are usually seen replaced by granulation tissue. Fibrosis in the submucosa can be classified as mild if early fibrosis was present, moderate if diffuse fibrosis was seen, and severe if there was diffuse fibrosis with hyalinization and atrophic changes in minor salivary glands and skeletal muscle. Chronic inflammatory cells (i.e., lymphocytes, plasma cells, and macrophages) are also seen. As reported in the literature, the risk of oral cancer developing in oral submucous fibrosis is 7.6% over a period of 10 years [23
]. Daftary reported that on followup, one third of his patients suffering from oral submucous fibrosis ultimately developing oral cancer [24
In summary all available treatments for oral submucous fibrosis are basically palliative in nature. Surgical procedures are indicated only in cases with advanced disease. A safe and simple mode of treatment such as steroid or enzymes injection along with proper habit restriction should be selected in the earlier stages of the disease. Early detection is key toward better prognosis and outcome.