USE OF ANTI OXIDANTS IN TREATMENT OF LEUKOPLAKIA

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INTRODUCTION

Leukoplakia is a white lesion of the oral mucosa particularly those that appear leathery and cannot be dislodged easily A white patch or plaque that cannot be characterized clinically or pathologically as any other disease- WHO collaboration (1978) At an international seminar on oral leukoplakia and an associated lesion related tobacco habit held in Malrno Sweedan in 1983 the proposal was made to modify the WHO collaborating reference center definition for leukoplakia to read

Leukoplakia is a whitish patch or plaque that cannot be characterized clinically or pathologically as any other disease and is not associated with any physical or chemical causative agent except the use of tobacco Total life time risk of malignant transformation is estimated to be 4-6% (Leurman H etal 1995) Lesions of the tongue and floor of the mouth account for more than 90% of cases that show dysplasia or carcinoma (Waldron etal 1975)

ETIOLOGY

A number of locally acting etiological agents including tobacco, alcohol,candidiasis habe been implicated as causative factors True leukoplakia is often related to tobacco usage (Axell T etal 1996) More than 80% of the leukoplakia are smokers, development of leukoplakia in smokers also depends on dose, duration of use as shown by heavy smokers having a more frequent incidence of lesion than light smokers Cessation of smoking often results in partial to total resolution of leukoplakia

Candidia aibicans is frequently found in histological section of leukoplakia and is consistently (60% of cases) identified in nodular leukoplakia but rarely in homogenous leukoplakia (3%) term candidia leukoplakia and hyper plastic candidiasis have been used to describe such lesions (Cawson etal 1988) Sun light is well known to be an etiologic factor for the formation of leukoplakia of vermilion border of the lower lip

CLINICAL FEATURES

Majority of leukoplakia are a symptomatic Development of carcinoma from leukoplakia has been reported to occur in 4-17.5% of patients with mean observation period ranging from 3.7 11.7yrs (Silverman etal 1984) Buccal mucosa are most frequently affected (Silver man etal1984) More commonly found in men, occurs in adults older than 50yrs of age prevalence increase rapidly with age especially for males and 8% of men older than 70yrs of age are affected

TYPES

HOMOGENOUS LEUKOPLAKIA: It has well defined patch, localized or extensive that is slightly elevated and that has a fissured wrinkled or corrugated surface on palpation these lesions may feel leathery to dry cracked mudlike NODULAR OR SPECKLED LEUKOPLAKIA It is a mixed red and white lesion in which white keratotic white nodules or patches are distributed over an atrophic erythematous back ground. This type of leukoplakia is associated with high malignant transformation rate

VERRUCOUS LEUKOPLAKIA

Thick white lesion with papillary surface in the oral cavity. These lesions are usually heavily keratinized and are most often seen in older age group PROLIFERATIVE VERRUCOUS LEUKOPLAKIA: They are verrucoid white plaques that tend to be slowly involve multiple mucosal sites in the oral cavity PVL has a very high risk of transformation to dysplasia, squamous cell carcinoma or verrucous carcinoma

HISTO PATHOLOGY

Benign form of leukoplakia are characterized by variable patterns of hyperkeratosis and chronic inflammation Waldron and Shafer in a land mark study of over 3,000 cases of leukoplakia, found that 80% of the lesions represented benign hyperkeratosis with or with out thickened spinous layer(acanthosis) About 17% of the leukoplakia shows dysplastic changes in the basal or parabasal zones of the epithelium

DIFFERENTIAL DIAGNOSIS

Lichen planus Leukoedema Lupus erythematosis White sponge nevus Verruca vulgaris Hairy leukoplakia Cheek biting

MANAGEMENT BY ANTI OXIDANTS

Antioxidants are the products which are derived mainly from green or colored vegetables food grains, animal fats and also from some spices like cucuramin (turmeric) or garlic The function of anti oxidants is to remove the free oxygen radical from the body and as a result prevents the cell damage or undergoing any carcinomatous changes Beta carotene, retinoic acid, ascorbic acid and alpha tocopherol are examples of anti oxidants

BETA CAROTENE

It is primarily found in the green vegetables, the deeper the color of vegetable or fruit greater the carotene content Approx 16% of the ingested beta carotene is transformed in to retinol with in the intestinal mucosa by a two step process that converts 6micro grams of BC into 1mm of retinol Fate of beta carotene after it reaches liver Very small amount can be converted in to retinol It can be incorporated in to very low densit lipo protein cholesterol Can be stored in liver

RELATION SHIP TO HUMAN CANCER

In dietary studies low beta carotene intake has been associated with an increased risk of lung, laryngeal, gastric, ovarian, breast, cervical and oral cancer Several studies have shown that a low intake of fruits and vegetables which are the primary source of beta carotene is also related to generalized increased cancer risk and mortality

THERAUPETIC USE OF ORAL LEUKOPLAKIA

RETINOL AND RETINOIDS

Vitamin A also known as retinol, is an alcohol that can be converted in to aldehyde or retinoic acid Retinol is found in dairy products, eggs and meats Silverman etal showed that doses exceeding 300,000 IU/day of vitamin A ester for more than 3mths can exceed liver storage capacity and cause side effects that include rashes, dry skin and pruritis Of more than 1500 synthetic analogues of vitamin A 13-cRA (isotretinoin) has generated the most interest

RELATIONSHIP TO HUMAN CANCER

The first study that associated Vitamin A deficiency with cancer appear in 1941 Low intake of Vitamin A has been linked with an increased risk of developing cancer of the lung, colon, breast, pharynx, larynx and bladder The theories proposed to explain Vitamin A include Deficiency of Vitamin A disturbs normal epithelial growth Tumor surveillance is dependent on levels of vitA Vitamin A directly influences gene expression

THERAPEUTIC USE OF ORAL LEUKOPLAKIA

ASCORBIC ACID

Ascorbic acid commonly known as Vitamin C, is found in citrus fruits, cruciferous vegetables The (RDA) recommended daily allowance range from 60mg/day for non smokers to 100mg/day for smokers It is because they have a decreased concentration of A.A in their serum and leukocytes It is reported that many people ingest more than 1gmof ascorbic acid per day with out any apparent ill effects

RELATIONSHIP WITH HUMAN CANCER

Numerous studies have shown that a low intake of AA is associated with increased of cancer of the stomach, esophagus, oral cavity The protective effect of dietary AA is more attributable to intake from fruits compared with vegetables Low serum level of AA have been associated with an increased risk of cancer, especially of the stomach

ALPHA-TOCOPHEROL

The most active and common form of Vitamin E Found in plant oils, wheat germ and green leafy vegetables The RDA for adult males is 10mg/day, and the average daily intake for adult males in USA is 11mg/day The absorption of AT ranges from 20% to 80%, and the efficiency decreases as the intake exceeds 30mg/day

RELATIONSHIP TO HUMAN CANCER

The patients with low serum level of AT had a relative risk of > 2.0 for gastrointestinal cancers The role of AT in cancer risk reduction is unclear, but the proposed mechanism includes The control of free radical damage Blockade of chemical reactions by mutagens or carcinogens Enhancement of detoxification Enhanced immune response

ANTI OXIDANT COMBINATIONS

THERAPEUTIC USE FOR LEUKOPLAKIA

CONCLUSION
The use of anti oxidant supplements has shown some promise but the predictability of success remains uncertain and long term results are un available Before the decision to use any antioxidant is made it is critical to obtain a histopathologic diagnosis of the lesion

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