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OROFACIAL MEDICINTidskrift för Svensk förening för Orofacial Medicin

Nr 2 årgång 2 2012

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IntroductionOral smokeless tobacco in the form of moist snuff (snus) has been used in Scandinavia, and especially in Sweden, for centu-ries (1). In Sweden, the snus habit has increased steadily during the last decades and among men it

is more prevalent than tobacco smoking (19)

Most often a snus pinch of loose snuff or a “tea-bag”-like sachet containing snus is placed in the vestibular area inside the upper lip (1). Almost invariably a mucosal change can be registered at the site of snus application (6). This change has been labelled snuff/snus-induced change or snuff-induced leukoplakia (17, 18). Snus-induced lesions have been categorized in four- or three grade scales according to their clinical appearance (7, 11). The snus induced lesions encountered

in Sweden have shown to be reversible after cessation of habit (16, 18), a finding supported by animal experiments (14).

The histological changes of snuff/snus-induced lesions have been extensively studied (2, 7, 10, 11, 15). In short, the lesions are characterised by increased epithelial thickness, vacuolated epithelial surface cells with a chevron type of keratinisation, a demarcated zone under the vacuolated cells, moderate in-flammation and sometimes an amorphous change of collagen in the connective tissues and also

Oral changes caused by tobacco free snuff

En 62-årig man remitterades för undersökning och behandling av en förändring i munslemhinnan innanför överläppen och som orsakats av en påsförpackad tobaksfri snusprodukt (ONICO®, Swedish Match). Såväl den kliniska som den histopatologiska bilden var identisk med den man finner vid förändringar orsakade av tobaksbaserade påsförpackade snusprodukter. Patienten ombads att under en treveckorsperiod ändra applikation av snuset från vänster till höger sida. Efter dessa tre veckor hade föränd-ringen helt försvunnit på vänster sida och en ny liknande den ursprungliga uppstått på höger sida.

TONY AXÉLL1, ULF ZÄTTERSTRÖM2, GUNNAR WARFVINGE3

1Maxillofacial Unit, Halmstad Hospital, Halmstad, Sweden, 2Dept of Oto-rhino-laryngology/Head and Neck Surgery, Rikshospitalet Medical Center, Oslo, Norway 3Dept of Oral Pathology, Faculty of Odontology, Malmö University, Malmö, Sweden.

Keywords: leukoplakia, smokeless tobacco, snuff, snuff-induced changes, snus

Corresponding author:Prof. Tony AxéllMaxillofacial UnitHalmstad HospitalSE-301 85 HalmstadSwedenTelephone: +46-35-120543 E-mail: tony.axell@telia.com

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salivary gland changes. These changes have been considered reactive (16).

In some reports possible factors or ingredients causing the snus/snuff-induced changes have been discussed, such as contents of tobacco-specific nitrosamines, contents of nicotine and pH value of products (5, 12). This report will illus-trate that tobacco may not be a necessary ingredient for the development of snuff-induced oral lesions.

CaseA 62 year old healthy man was referred for examination of an oral mucosal change to the left side inside the upper lip. The le-sion was compatible with a snuff-induced lesion of degree 2-3 (7). For about one and a half year he had regularly placed tobacco-free snuff (brand ONICO®, Swedish Match) at the site of the change. This tobacco-free and nicotine-free snuff product is delivered in portion sachets. A 50 gram box was consumed within 2-3 days and the sachets were used all day long. Before using this product he had used tobacco containing snuff sachets (brand General White®, Swedish Match) for a period of 2-3 years and placed it on the same site as the present site of change. The lesion was photo-graphed (Fig. 1) and a 6 mm punch biopsy was secured for histological analysis. The biopsy displayed histological changes indistinguishable from those described in snus-induced le-sions (2, 7). Hence, the surface epithelium was slightly thick-

ened with a conspicuously oe-dematous superficial layer that showed a tendency to chevron type of keratinisation (Fig. 2). The affected zone was sharply demarcated from the normal epithelium underneath. The rete ridges were somewhat broadened and irregular and occasional mitoses were identified but the epithelium was otherwise well differentiated without evidence of dysplasia. Only few mono-nuclear cells appeared in the adjacent lamina propria. After the initial examina-tion the patient switched site of application, from the left to the right side, and with unchanged consumption pattern. At re-examination three weeks later the lesion at the left side had resolved completely while a de-gree 2-3 snuff-induced lesion was registered on the right side inside the upper lip i.e. the site were the sachets had been regularly placed during the three weeks of follow-up (Fig. 3 a-c). Products used by the patientGeneral white® – finely cut air-dried and pasteurisized tobacco of type Virginia, salts, humectants and flavors. Water contents: 50%, pH value: 8.0, sachet material: cottonONICO® – dried and finely cut corn fibers, salts, humectants and flavours.Water contents: 50%, pH value: 8.0, sachet material: cotton

DiscussionSnuff induced lesions have also been labelled snuff leukoplakia holding out the prospect of a pre-cancerous/potentially malignant

trait. However, at international meetings it has been suggested that a snuff (quid) induced lesion should be classified as a separate clinical entity and thus not as a leukoplakia (8, 20). Further, in the only longitudinal follow-up study on snuff (snus) induced le-sions in Scandinavia no increased risk was found for such lesions to develop into cancer (18). The pathogenesis behind lesions presented with tobacco-free snus products could be speculated upon. Concerning tobacco content products it is logic to assume that tobacco/nicotine should be important for the development of a lesion. However, the amount of nicotine contents did not seem to have an impact on the development of oral mucosal lesions (3, 4). Alternatively, the pH value of the quid placed at the mucosa could have an impact on the de-velopment. Interestingly, the pH value was about 8.0 for both of the products that had been used by the patient in our report i.e. the previously used tobacco product General White® and later, the tobacco-free and nicotine-free product ONICO®. The clinical as well as the pathological picture points at a nature of caustic lesion. Thus, the lesion in the vestibular area inside the upper lip in the present case has characteristics close to lesions caused by caus-tic substances. This might also explain the surprisingly rapid healing and appearance of a new lesion within a very short time presented at this report. Another possible expla-nation for the lesion might be frictional irritation of the quid

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on the oral mucosa. Jagged teeth, cheek and lip biting, or overextended prostheses are known causes of such lesions (9). Snus is put in the frontal part of the upper gingival fold and it may be speculated that a relative dryness of this part of the mouth makes the mucosa more vulnerable to mechanical insults. The tobacco-free and nicotine-free snuff product ONICO® that caused the present lesion consists of a mixture of plant (corn) fibers, salts, humectants and flavors contained in a por-tion sachet. The structure of the sachet material itself might be of interest. For example, a rough and semi-dry foreign body may cause more adherence and mechanical stress on the adjacent mucosa than a smooth and lubricated one. Another explanation may be that the tobacco-containing as well as tobacco-free products may contain other irritating

substances such as flavours. The morphology of the lesion, however, did not sup-port frictional irritation as a causative mechanism. Thus, the surface epithelium was slightly thickened with a marked oe-dematous superficial layer that showed a tendency to chevron type of keratinisation (Fig. 2). In contrast, histology in frictional white lesions is expected to show hyperkeratinisation without vacuolization. From a clinical point of view the lesion caused by ONICO® is more similar to changes caused by acidic prepa-rations such as Nelex®, desinfec-tants such as chlorhexidine or dentifrices containing sodium lauryl sulphate (13). Finally, it may be argued that the lesion encountered in this case after use of ONICO® might be a sustained lesion after use of tobacco containing snus. However, it has repeatedly

been shown that such a lesion vanishes after a short period of time after cessation of use (14, 16). The initial lesion registered in this report should thus not have anything to do with the snus product used more than one year ago. This argumentation is supported by the finding of a rapid and complete healing after cessation of snus application after a few weeks.

ConclusionSnuff (snus) induced lesions could be caused by tobacco- and nicotine-free products. Such lesions seem to be reversible at cessation of habit and may ap-pear within a few weeks after the application of the snuff quid. Most likely, the change is related to the pH value of the product possibly with an added effect of frictional irritation and irritation from flavours.

Fig. 1. Snuff-induced change degree 2-3 to the left inside the upper lip

Fig. 2a. Section from lip mucosa exposed to tobacco-free snuff for three weeks. The epithelial surface displays a characteristic, sharply demarcated oedema with slight chevron type of keratinisation. The rete ridges are somewhat irregular. No evident inflammation. (H & E, ×10)

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Fig. 2b. Same lesion as in Fig. 2a. Picture showing the transition zone between oedematous and normal portions of the epithelium. The affected cells are vacuolated and some contain remnants of non-viable nuclei. (H & E, ×40)

Fig. 3a. Mucosa without changes on the leftside and with a snuff-induced change degree2-3 on the right side inside the upper lipafter switch of application site of tobacco-free snuff from left to right side.

Fig. 3b. Detailed photo of healthy mucosa on the left side where no snuff was placed during a three week period.

Fig. 3c. Detailed photo of snuff-induced lesion degree 2-3 on the right side where tobacco- free snuff was placed for a three-week period.

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