Oral submucous fibrosis

Abstract: Data from recent epidemiological studies provide overwhelming evidence that areca nut is the main aetiological factor for OSF. A clear dose-dependent relationship was observed for both frequency and duration of chewing areca nut (without tobacco) in the development of OSF. Commercially freeze dried products such as pan masala, Guthka and mawa (areca and lime) have high concentrates of areca nut per chew and appear to cause OSF more rapidly than by self prepared conventional betel quid that contain smaller amounts of areca nut. It is logical to hypothesise that the increased collagen synthesis or reduced collagen degradation as possible mechanisms in the development of the disease. There are numerous biological pathways involved in the above processes and, it is likely that the normal regulatory mechanisms are either down regulated or up regulated at different stages of the disease. Among the chemical constituents, alkaloids from areca nut are the most important biologically whilst tannin may have a synergistic role. These chemicals appear to interfere with the molecular processes of deposition and/or degradation of extracellular matrix molecules such as collagen. In vitro studies on human fibroblasts using areca extracts or chemically purified arecoline support the theory of fibroblastic proliferation and increased collagen formation that is also demonstrable histologically in human OSF tissues. The copper content of areca nut is high and the possible role of copper as a mediator of fibrosis is supported by the demonstration of up regulation of lysyl oxidase in OSF biopsies. It has been postulated that areca nut may also induce the development of the disease by increased levels of cytokines in the lamina propria. Increased and continuous deposition of extracellular matrix may take place as a result of disruption of the equilibrium between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMP). Current evidence implicates collagen-related genes in the susceptibility and pathogenesis of OSF. The individual mechanisms operating at various stages of the disease-initial, intermediate and advanced-need further study in order to propose appropriate therapeutic interventions.

Abstract: On the basis of the literature and personal experience, we have discussed a pcculiar oral disease—submucous fibrosis—seen mainly among East Indians. The condition is chronic and is clinically characterized by blanching and stiffness of the oral mucosa. Histologically, the oral connective tissue becomes hyalinized and the overlying epithelium markedly atrophic. The disease may be due to an irritant (chili?), acting over a long period of time. Evidence is presented that submucous fibrosis may be considered an important precancerous condition in Southeast Asia.

Abstract: South Asia is a major producer and net exporter of tobacco. Over one-third of tobacco consumed regionally is smokeless. Traditional forms like betel quid, tobacco with lime and tobacco tooth powder are commonly used and the use of new products is increasing, not only among men but also among children, teenagers, women of reproductive age, medical and dental students and in the South Asian diaspora. Smokeless tobacco users studied prospectively in India had age-adjusted relative risks for premature mortality of 1.2-1.96 (men) and 1.3 (women). Current male chewers of betel quid with tobacco in case-control studies in India had relative risks of oral cancer varying between 1.8-5.8 and relative risks for oesophageal cancer of 2.1-3.2. Oral submucous fibrosis is increasing due to the use of processed areca nut products, many containing tobacco. Pregnant women in India who used smokeless tobacco have a threefold increased risk of stillbirth and a two- to threefold increased risk of having a low birthweight infant. In recent years, several states in India have banned the sale, manufacture and storage of gutka, a smokeless tobacco product containing areca nut. In May 2003 in India, the Tobacco Products Bill 2001 was enacted to regulate the promotion and sale of all tobacco products. In two large-scale educational interventions in India, sizable proportions of tobacco users quit during 5-10 years of follow-up and incidence rates of oral leukoplakia measured in one study fell in the intervention cohort. Tobacco education must be imparted through schools, existing government health programmes and hospital outreach programmes.

Abstract: In south-east Asia, Taiwan and Papua New Guinea, smoking, alcohol consumption and chewing of betel quid with or without tobacco or areca nut with or without tobacco are the predominant causes of oral cancer. In most areas, betel quid consists of a mixture of areca nut, slaked lime, catechu and several condiments according to taste, wrapped in a betel leaf. Almost all habitual chewers use tobacco with or without the betel quid. In the last few decades, small, attractive and inexpensive sachets of betel quid substitutes have become widely available. Aggressively advertised and marketed, often claimed to be safer products, they are consumed by the very young and old alike, particularly in India, but also among migrant populations from these areas world wide. The product is basically a flavoured and sweetened dry mixture of areca nut, catechu and slaked lime with tobacco (gutkha) or without tobacco (pan masala). These products have been strongly implicated in the recent increase in the incidence of oral submucous fibrosis, especially in the very young, even after a short period of use. This precancerous lesion, which has a high rate of malignant transformation, is extremely debilitating and has no known cure. The use of tobacco with lime, betel quid with tobacco, betel quid without tobacco and areca nut have been classified as carcinogenic to humans. As gutkha and pan masala are mixtures of several of these ingredients, their carcinogenic affect can be surmised. We review evidence that strongly supports causative mechanisms for genotoxicity and carcinogenicity of these substitute products. Although some recent curbs have been put on the manufacture and sale of these products, urgent action is needed to permanently ban gutkha and pan masala, together with the other established oral cancer-causing tobacco products. Further, education to reduce or eliminate home-made preparations needs to be accelerated.