Oral lesions that associated with Tobacco use

Effect of Tobacco in oral mucosa

1. tobacco induced oral mucosal lesions By Ahmed Saleem

2. What is Tobacco? Tobacco is a plant originally indigenous to the Americas which is now grown across the world. Its leaves contain high levels of the addictive chemical nicotine and many cancer-causing chemicals, especially polyaromatic hydrocarbons (PAHs ). The leaves may be smoked (in cigarettes, cigars, and pipes), applied to the gums (as dipping and chewing tobacco), or inhaled (as snuff). Tobacco use and exposure to second-hand tobacco smoke causes many types of cancer, as well as heart, respiratory, and other diseases.

3. Harmful Chemicals in Tobacco Products 1.Tobacco smoke Tobacco smoke is made up of thousands of chemicals, including at least 70 chemicals known to cause cancer Some of the chemicals found in tobacco smoke include:  Hydrogen cyanide Formaldehyde Lead Arsenic Ammonia Benzene Carbon monoxide Tobacco-specific nitrosamines (TSNAs) Polycyclic aromatic hydrocarbons (PAHs) Radioactive elements, such as polonium-210 Most of the substances come from the burning tobacco leaves themselves, not from additives included in cigarettes .  (American Cancer Society)

4. Radioactive materials in tobacco smoke Radioactive materials are in the tobacco leaves come from the fertilizer and soil used to grow the tobacco leaves, so the amount in tobacco depends on the soil the plants were grown in and the type of fertilizers used. These radioactive materials are given off in the smoke when tobacco is burned, which smokers take into their lungs as they inhale, and this may be more associated smokers getting lung cancer. (American Cancer Society)

5. Smokeless tobacco products Smokeless tobacco products contain a variety of potentially harmful chemicals, including high levels of Tobacco-specific nitrosamines (TSNAs). There are also other cancer-causing agents in smokeless tobacco, such as polonium-210 (a radioactive element) and other polycyclic aromatic hydrocarbons (PAHs). These carcinogens are absorbed through the mouth and may be why several types of cancer are linked to the use of smokeless tobacco. On average, smokeless tobacco products kill fewer people than cigarettes . But while they're often promoted as a less harmful alternative to smoking, some types have still been linked with cancer. No smokeless tobacco product has been proven to help smokers quit. (American Cancer Society)

6. E-cigarettes and similar devices E-cigarettes and other electronic nicotine delivery systems (ENDS) have become very popular in recent years, especially among younger people. Makers of e-cigarettes and other electronic nicotine delivery systems (ENDS) often claim the ingredients are safe. But the aerosols that these products produce can contain nicotine, flavourings, and a variety of other chemicals , some known to be toxic or to cause cancer. The levels of many of these substances appear to be lower than in traditional cigarettes , but the amounts of nicotine and other substances in these products can vary widely because they are not standardized. The long-term health effects of these devices aren't yet known.  (American Cancer Society)

7. SMOKLESS TOBACCO Smokeless tobacco / spit tobacco / chewing tobacco. Mainly two forms: snuff and chewing tobacco . Snuff – users ; between their lower lip and gum. Chewing tobacco - users put between their cheek and gum. The tobacco juice is sucked and chewed - nicotine -absorbed into the bloodstream through the oral tissues.

8. CONSUMTION • Chewed : gutkha , pan, mawa , mainpuri tobacco, khaini, zarda • Applied on gums and teeth : mishri , gudhaku , bajjar , tooth paste • Inhaled : snuff

9. TYPES OF SMOKELESS TOBACCO • Gutkha • Khaini • Mainpuri tobacco • Mawa • Mishri • Paan • Snuff • Zarda

10. GUTKHA • Main component - arecanut along with tobacco . KHAINI Paste of tobacco + slaked lime & is used with arecanut . Mixed with the thumb to make the mixture alkaline-premolar region of mandibular groove. ZARDA • Tobacco leaves + lime+spices – boiled in water. • Residual tobacco –dried & coloured.

11. MAINPURI TOBACCO • Tobacco+ slaked lime + finely cut arecanut + camphor + cloves. • Mainly-Uttar Pradesh. • High incidence of oral cancer & leukoplakia. MAWA Gujarathi preparation made from shavings of arecanut , tobacco and slaked lime. Mixed & chewed excessively and kept in mandibular groove- causes oral cancer.

12. MISHRI         Prepared by roasting tobacco on a hot metal plate-black- powdered-used with catechu. Used to clean teeth. PAN (BETEL QUID) WITH TOBACCO • Most common-ancient habit. • Betel leaf + arecanut + slaked lime + catechu. • Arecanut -vital component-drastically affects oral health. • Contains nitrosamines-carcinogenic. • Pan masala - mainly contains tobacco - causes oral cancer.

13. SNUFF • Finely powdered air-cured & fire-cured tobacco leaves. • Used orally/nasally. • Carried in a metal container-a twig is dipped into it-placed in oral vestibule. • Causes oral squamous cell carcinoma.

14. CONTENTS IN THE TOBACCO: • Nitrosamines • Polycyclic aromatic hydrocarbons • Nitrasoproline • Polonium IN THE TOBACCO SMOKE: Carbon monoxide • Thiocyanate • Hydrogen cyanide • Nicotine

15. ROLE OF CONSTITUETION OF TOBACCO Polycyclic aromatic hydrocarbons • Nicotine carcinogenesis • Nitrosamine • Phenol tumour promotion& irritation • Benzopyrene • Carbon monoxide - impaired oxygen transport • Formaldehyde & oxides of N - toxicity

16. People can smoke, chew, or sniff tobacco. Smoked tobacco products include cigarettes, cigars, bidis, and kreteks. Some people also smoke loose tobacco in a pipe or hookah (water pipe). Chewed tobacco products include chewing tobacco, snuff, dip, and snus; snuff can also be sniffed. Tobacco consumption also remains the most important avoidable risk factor for oral cancer. Tobacco related cancers account for nearly 50% of all cancers in men and 25% in women .

17. prevalence Children: Approximately 43 million children (aged 13-15) used tobacco in 2018 (14 million girls and 29 million boys). Globally, 942 million men and 175 million women ages 15 or older are current smokers. Most gains are being made in low- and middle-income countries. WHO’s South East Asian Region has the highest rates of tobacco use, of more than 45% of males and females aged 15 years and over.

18. What are vaping devices? Vaping devices, also known as e-cigarettes, e-vaporizers, or electronic nicotine delivery systems, are battery-operated devices that people use to inhale an aerosol, which typically contains nicotine (though not always), flavorings , and other chemicals. They can resemble traditional tobacco cigarettes  (cig-a-likes) , cigars, or pipes, or even everyday items like pens or USB memory sticks. Other devices, such as those with fillable tanks, may look different. Regardless of their design and appearance, these devices generally operate in a similar manner and are made of similar components. More than 460 different e-cigarette brands are currently on the market. 1  Some common nicknames for e-cigarettes are: ( e-cigs, e-hookahs, hookah pens, vapes, vape pens, mods (customizable, more powerful vaporizers)).

19. Tobacco Induced Oral Mucosal Lesions Long term contact of tobacco with the oral mucosa induces variety of changes which could be due to the carcinogen itself or as a protective mechanism of the oral cavity. These changes could be categorized as tobacco induced oral mucosal lesions which are less likely to cause cancer, lesions that are potentially malignant and tobacco induced malignancies .

20. Tobacco Induced Non-Neoplastic Oral Mucosal Lesions

21. Betel chewer’s mucosa Betel chewer’s mucosa was first described in 1971 by (Mehta et al). It is a clinical appearance, which characterised by a brownish‐red discolouration of the oral mucosa with an irregular epithelial surface that has a tendency to desquamate or peel off. The lesion might occur at the site of quid placement (buccal mucosa), because of either the direct action of quid or traumatic effect of chewing or both with a tendency for the oral mucosa to desquamate or peel. The underlying areas assume a pseudomembranous or wrinkled appearance. The bright red colour produced by betel chewing is due to the formation of O-quinone from the water-soluble polyphenols notably leucocyanidins at alkaline pH of 8 to 9 via secondary reactions .

22. The prevalence of Betel chewer’s mucosa varies between 0.2% and 60% in different studies from South and Southeast Asia. Women are more frequently affected than men. Betel chewer's mucosa may be found together with other oral mucosal lesions such as leukoedema , leukoplakia and ulceration

23. The histological features are characteristic: The epithelium is often hyperplastic , and brownish amorphous material derived from the betel quid may be demonstrated not only on the epithelial surface but also intra‐ and inter ‐cellularly + Ballooning of epithelial cells may occur. . Betel chewer's mucosa is most likely not associated with oral cancer. Differential diagnoses include: cheek biting, with which it has a number of similarities, and other predominantly white lesions that may have taken up stains from tobacco and other substances.

24. Leukoedema Leukoedema is a chronic white mucosal condition in which the oral mucosa has a grey opaque appearance , and when the mucosa is stretched the lesions disappear and reappear on releasing the mucosa. It develops due to piling of spongy cells . Leukoedema is the normal anatomic variant of the oral mucosa which has clinical appearance similar to potentially malignant white lesions such as leukoplakia and lichen planus. Other lesions which closely mimic leukoedema are white sponge nevus and cheek bite. Its association with smoking habit is unclear .

25. Histopathological examination: reveals hyper parakeratosis and acanthosis of surface epithelium. Cells of the spinous layer show intracellular oedema, cells appear pale and have pyknotic nucleus. No dysplastic features were observed.

26. No treatment is required for leukoedema, although topical application of tretinoin has shown a promising result in symptomatic cases.

27. Nicotine Stomatitis Smoker’s palate is also known as leukokeratosis nicotina palate , Nicotine Stomatitis, Smoker's Palate, Smoker's Keratosis, Smoker's  Patch) and is a common reaction of palatal mucosa to smoking. Clinically the lesion appear as diffuse white patch with numerous excrescences having central red dots corresponding to minor salivary gland ducts. Nicotinic Stomatitis  is been associated with pipe, cigarette, and cigar smoking, and, rarely, with chronic ingestion of high-temperature liquids (these changes are observed most often in pipe and reverse cigarette smokers and less often in cigarette and cigar smokers). Generally, it is asymptomatic or mildly irritating , Patients typically report that they are either unaware of the lesion or have had it for many years without changes.  

28. Nicotinic Stomatitis  first becomes visible as a reddened area and slowly progresses to a white ( cannot be wiped off), thickened, and fissured appearance. The roof of the mouth has numerous minor salivary glands, they become swollen, and the orifices become prominent, giving the tissue a speckled white and red appearance.

29. The mechanism of action is heat irritation from a tobacco product that acts as a local irritant, stimulating a reactive process (In patients who wear dentures often protect the palate from these irritants). Management: Nicotinic Stomatitis  generally is a reversible lesion once the irritant (that is, smoking) is removed. The prognosis is excellent .

30. Lichenoid lesions Lichenoid lesions grossly resemble oral lichen planus but have certain specific differences: The lesion is characterized by the presence of fine, white, wavy parallel lines that do not overlap or criss-cross, is not elevated and in some instances radiate from a central erythematous area . The lesion generally occurs at the site of quid placement . Some 89% of the lesions occur among betel quid chewers and 11% among those who chewed pan and smoked tobacco . Most of these lesions remain stationary or sometimes regress on discontinuance of the habit thereby requiring no further treatment. Sufficient epidemiological data is unavailable regarding this lesion.

31. The lesions of OLL resemble those of oral lichen planus (OLP), and it is therefore necessary to exclude likely OLLs when making a diagnosis of OLP (While some authors do not differentiate the two). OLP is a more widespread condition involving many anatomical sites within the oral cavity (or elsewhere including skin and genitalia ). Both OLP and OLL can be considered potentially malignant. Typically the clinical presentation in both conditions can be reticular white patches, papules, or plaques with or without erosions or ulcerated areas. The clinical diagnosis is further complicated because similar oral lesions can occur as a result of drug-related lichenoid reactions or as graft versus host disease (GVHD), discoid lupus erythematosus (DLE), and systemic lupus erythematosus (SLE). These conditions too have a similar clinical appearance. Diagnosis is facilitated by detailed history, clinical findings, and immunohistology findings : OLLs they are usually unilateral and not symmetrical. They are most commonly seen on the buccal mucosae and tongue. The gingivae, palate, or floor of mouth are rarely affected, and patients almost never have associated cutaneous symptoms.

32. management Diagnosis is facilitated by detailed history, clinical findings, and immunohistology findings. Clinically: OLLs they are usually unilateral and not symmetrical. They are most commonly seen on the buccal mucosae and tongue. The gingivae, palate, or floor of mouth are rarely affected, and patients almost never have associated cutaneous symptoms.

33. Difference between classic LICHEN PLANUS and LICHENOID LESION LICHEN PLANUS LICHENOID LESION Age Mean age 50 years Mean age 66 years Site Intra+ extra orally Associated with the cause Histology Comact hyperkeratosis Wedge shaped hypogranulosis Irregular acanthosis “saw-toothing” of rete ridges and vascular damage to the basal layer. A dense band like infiltration of lymphocytes. Focal parakeratosis and focal absence of granular layer Colloid bodies are more numerous and are present higher up in the epidermis. The interface infiltration is less dense and more pleomorphic with abundant plasma cells and eosinophils. Treatment First line corticosteroid Withdrawal of the cause.

34. Histologically: In 1973 ( Pinkus ) invent the term “lichenoid tissue reaction” to describe the histological pattern featuring damage to keratinocytes(apoptosis) , infiltrate of inflammatory cells in the connective tissue which may extend into the epithelium and keratosis or hyperkeratosis. He described this histopathological pattern common to several diseases referred to above rather than a clinical entity. Since then, further histological features have been identified by ( Schiodt ) to distinguish, for example, oral DLE from OLP, namely, keratin plugging , atrophy of the rete processes , a deep inflammatory infiltrate , oedema in the lamina propria , and a thick PAS deposit in the basement membrane zone . It has also been suggested that a mixed cell subepithelial infiltrate and a deeper diffuse distribution in lamina propria can help to distinguish a lichenoid lesion. Distinguishing between OLP and OLL remains a challenge. A study carried out by Thornhill et al confirmed the difficulty of making the distinction between OLL and OLP on purely histological grounds. Overall the pathologists were able to distinguish between the two conditions only a third of the time. Most pathologists report it is either OLP or OLL.

35. Oral pigmentation (SMOKER’S MELANOSIS) Oral pigmentation secondary to smoking may occur occurs as diffuse pigmentation at any site with increased tendency to affect facial gingiva . The frequency of the lesions increases with heavy usage of cigarette smoke. Different studies show prevalence rates of 3.5%,1.14%, 2.3% and 4.17%. But most of the studies have reported smokers’ melanosis as the most frequently encountered oral mucosal lesion . Aetiology and Pathogenesis: It has been suggested that melanin production in the oral mucosa of smokers serves as a protective response against some of the harmful substances in tobacco smoke. Clinical features: It occurs as diffuse pigmentation frequently. Diagnosis: is made based on the clinical appearance and history of tobacco use. Management: There is no specific treatment for the condition, cessation of smoking usually resolves the pigmentation with time.

36. Tobacco Induced potentially malignant

37. Leukoplakia Leukoplakia defined by WHO as a predominantly white lesion or plaque affecting the oral mucosa that cannot be characterized clinically or histopathologically as any other disease and is not associated with any other physical or chemical agents except tobacco . The prevalence of oral leukoplakia= 2% Leukoplakia is 6 times more common in tobacco user in compare to non-users.

38. Leukoplakia is the term used to recognize white plaques of questionable risk having excluded other known diseases or disorders ?

39. Management of leukoplakia A biopsy is mandatory, and the definitive diagnosis is made when any etiological cause other than tobacco/areca nut use has been excluded and histopathology has not confirmed any other specific disorder. Leucoplakia is considered as a potentially malignant disorder with a malignancy conversion rate ranging from 0.1% to 17.5%. ( Carrard & van der Waal, 2018)

40. Erythroplakia. (Holmstrup, 2018) Erythroplakia is an uncommon but severe form of a potentially malignant lesion, defined by WHO as “any lesion of the oral mucosa that presents as bright red velvety plaques which cannot be characterized clinically or histopathologically as any other recognizable condition” According to the  American Academy of Oral Medicine , Erythroplakia and leukoplakia are generally considered precancerous (or potentially cancerous) lesions. the most common site affected is mucosal surfaces of the soft palate, the floor of the mouth, and the buccal mucosa. (Shafer and Waldron )  reported gender-related differences in terms of the mucosal sites affected; these investigators indicated that the most common site of occurrence of erythroplakia in men was the floor of the mou th, while in women , the combined mandibular alveolar mucosa, mandibular gingiva, and mandibular sulcus were most affected sites . Clinically, the lesion is thereby easily distinguishable from other red lesions of the oral mucosa including (Atrophic lichen planus lesions or Erythematous candidiasis).

41. PREVALENCE There appear to be few data available on the prevalence of oral erythroplakia, and most data are established in selected groups of individuals including hospital associated populations and samples of individuals with special habits. Most of the studies with epidemiologic data concerning oral erythroplakia were conducted in India and Southeast Asia, indicating prevalence rates of 0.02% to 0.83%, with the majority occurring in older individuals (sixth and seventh decades). A clinical hospital- based study of 500 patients (only one woman), all of whom were habitual psychoactive substance users, showed a prevalence of 0.6% ( Thavarajah et al., 2006), and the prevalence is almost similar (0.7% ) among 559 tobacco users (25% women) in Saudi Arabia (Al- Attas , Ibrahim, Amer, Darwish Zel, & Hassan, 2014), but among 210 addiction treatment centre residents (30% women) in southern Ireland, as 1.9% (O’Sullivan, 2011). In general population samples outside the hospital environment, the prevalence is found to be lower. Among 1241 individuals (47.1% women) in India, the prevalence of erythroplakia was 0.24% (Kumar et al., 2015), and a similar prevalence ( 0.3%) was found among 1385 rural Brazilian workers, of which 53.2% were females (Ferreira et al., 2016).

42. management Definitive treatment is by surgical excision, because it reduces malignant transformation but does not totally eliminate the risk. (In recent years, studies on the use of topical 5-aminolevulinic acid-mediated photodynamic therapy for oral erythro-leukoplakia have shown that this specific treatment exhibited partial to complete response after an average of three to six treatments. Still, neither long-term follow-up nor long- term results are provided. (Schmidt- Westhausen , 2017) It is well established that premalignant lesions may recur after surgical removal (Holmstrup et al., 2006; Lumerman , but cases of reversible erythroplakia have also been observed in a longitudinal study in which some lesions resolved without no treatment being offered (Holmstrup et al., 2006). Malignancy rates from 14% to 50% ( Reichart & Philipsen , 2005). Unfortunately, there is currently no reliable diagnostic tool to identify exactly those lesions that will progress to cancer and to obtain the best possible prognosis, patients with the lesions mentioned (sharply demarcated fiery red lesions situated at a slightly lower level) should therefore be followed intensely at short intervals independent of possible relation to other diseases or irritants

43. Palatal changes among reverse smokers Palatal changes secondary to reverse chutta smoking can be categorized as palatal keratosis, excrescences, patches, red areas, ulceration and pigmentation changes . These changes are seen in up to 46% of reverse smokers and carry increased tendency for malignant transformation ( No enough epidemiological data exist regarding the prevalence of these changes ).

44. Oral submucous fibrosis OSMF as a potentially malignant disease was first described in 1950’s with increased tendency to affect people of Asian descent . It is a chronic disorder characterized by fibrosis of the lining mucosa of the upper digestive tract involving the oral cavity, oro -and hypopharynx and the upper third of oesophagus. The fibrosis involves the lamina propria and the submucosa and may extend into the underlying musculature resulting in the deposition of dense fibrous bands , resulting in limited mouth opening . Areca nut has been proved to be the single most important etiological factor responsible for OSMF. The pre-cancerous nature was first described by (Paymaster) in 1956 that was later confirmed by various studies. A malignant transformation rate was shown to be in the range of 7 to 13% and (transformation rate of 7.6% was reported in cohort study)

45. The pre-cancerous nature was first described by (Paymaster) in 1956 that was later confirmed by various studies. A malignant transformation rate was shown to be in the range of 7% to 13% and a transformation rate of 7.6% was reported in cohort study. Previous data indicated that the prevalence of OSMF was in the range of 0.03% to 3.2% .

46. Lichen planus Lichen planus is a mucocutaneous disorder affecting the skin and mucous membrane with increased potential for malignant transformation. The condition most commonly affects individuals in the 5th to 6th decade although younger individuals are also affected and is twice more common in women than in men. The malignant potential of lichen planus has been a subject of intense research with studies showing malignant transformation in the range of 0 to 12.5% (Other reports put the overall prevalence rate at 0.5 to 2.2%).

47. The clinical features present as reticular, papular , plaque-like (hyperkeratotic variants) and erythematous, ulcerative, erosive, as well as bullous (erosive variants) forms. The reticular alteration has a web-like appearance and is the most common form (Wickham striae). OLP generally affects both sides of the buccal mucosa, frequently involving the tongue, gingiva, oral vestibule, or multiple locations of the oral mucosa, whereas manifestations on the palate are rare. In most cases, the clinical manifestations of OLP are sufficient for establishing the diagnosis, although a biopsy is recommended to confirm the clinical diagnosis and to exclude the presence of dysplasia or malignancy. Persistent erosive and plaque-like variants, especially involving the tongue, have a greater malignant potential. Symptomatic OLP is a painful condition and complete remission is rare. The symptomatic forms of OLP include the erosive, ulcerative, bullous, and erythematous variants (which manifest with symptoms such as a burning sensation and a considerable interference with food intake and daily oral hygiene).