Limited mouth opening in oral submucous fibrosis: reasons, ramifications, and remedies

Abstract

Limited mouth opening (LMO) in oral submucous fibrosis (OSF) has been attributed to both the submucosal and muscle fibrosis (MF). While reflectory trismus was proposed before as an auxiliary mechanism by another group, the stretch-mediated muscle damage (MSD), histopathological changes in blood vessels (such as endothelial dysfunction, endothelial hypertrophy, and endarteritis obliterans), and upregulated anaerobic isoforms of lactate dehydrogenase (LDH) have been proposed by us as complementary events leading to MF. Additionally, the amount of hypoxia-mediated upregulation of anaerobic isoforms of LDH determines the extent of MF. Radiotherapy (RT)-mediated release of reactive oxygen species causes vascular damage thereby worsening hypoxia. While the alteration in LDH levels secondary to hypoxia enhances fibrosis, RT worsens it. Oral squamous cell carcinoma occurring in the background of OSF is an absolute contraindication for RT as it augurs unfavorable prognosis. An algorithm to demonstrate this with evidence is clearly depicted. The role of HIF-1α in the progression of OSF and its malignant transformation, and the consideration of hyperbaric oxygen therapy as a therapeutic remedy in OSF are underscored.

LncRNA LINC00974 activates TGF‐β/Smad signaling to promote oral fibrogenesis

“…Epidemiological investigation has revealed that the habit of areca nut chewing is a major etiology factor for OSF development . One of the recent studies has shown that the limited mouth opening is mediated through numerous mechanisms, and TGF‐β is involved in several events, such as myofibroblast transdifferentiation . It is well known that persistent activation of myofibroblasts results in excessive accumulation of extracellular matrix (ECM), which contributes to the pathogenesis of fibrosis .…”

Aloe vera in treatment of oral submucous fibrosis: A systematic review and meta‐analysis

“…(a) Study design: Randomized control trials (RCTs); (b) Participants: Individual in any age group, diagnosed clinically and/or histopathologically with OSF; (c) Intervention: Aleo vera administrated topically and/or systemically; (d) Comparator: Any medical interventions (systemic, submucosal injection or topical agents), or a placebo control; (e) Outcomes: The primary outcomes included (i) subjective improvement in severity of mucosal pain/burning sensation, using any recognized validated pain scale, (ii) objective changes or improvement in maximal interincisal mouth opening, (iii) objective changes in tongue movement (protrusion), and objective changes in cheek flexibility, and the secondary outcomes included side effects of the intervention; (f) Language: articles published in English language.…”

“…Hence, OSF is predominantly seen in population groups from South and Southeast Asia . OSF usually affects young individuals aged 20‐40 years old, with a striking male predilection, and an estimated prevalence of 6.42 per 1000 . The disease process is characterized by juxta‐epithelial inflammatory reaction in the oral mucosa, fibro‐elastic change of lamina propria and epithelial atrophy .…”

“…The disease process is characterized by juxta‐epithelial inflammatory reaction in the oral mucosa, fibro‐elastic change of lamina propria and epithelial atrophy . Typically, the disease causes significant functional morbidity that include pain/burning sensation, vesicle formation, hypo‐mobility of soft palate and tongue, loss of taste sensation, intolerance to spicy foods, speech and swallowing problems and, severe limitation in mouth opening . Altogether, the condition has devastating effects that severely impair the patient's quality of life …”

Resveratrol (3,5,4′-trihydroxystilbene) and its properties in oral diseases

“…Moderate-to-severe OSF is irreversible and current treatment strategies include injections or topical application of steroids, oral subministration of lycopene (16 mg daily) and pentoxyfilline (400 mg 3 times daily) (16,118,119). A previous study demonstrated that RSV epigenetically inhibits Zinc finger E-Box binding homeobox 1 expression to suppress the myofibroblast activity of fibrotic buccal mucosal fibroblasts, and may serve as a dietary supplement for OSF patients (120).…”