Maysara Al-Shawaf, BDS, MSii Otu Nartey, BDS, MSc
King Saud University, College of Dentistry, P.O. Box 60169, Riyadh 11545, Saudi Arabia

 
The habit of chewing khat (Catha edulis) for its euphoric effect has been historically limited to east Africa and southwestern Arabian Peninsula. Two cases of severe oral mucosal ulcerations which occurred after chewing khat are reported. The histopathological examinations of specimens from both patients revealed microscopic features which were considered as a typical lichen planus or lichenoid drug eruption.

 
Khat (Catha edulis), a seedless plant, is indigenous and limited to certain parts of east Africa and the southwestern Arabian Peninsula. The young leaves of the plant are most favored because they are more potent and tender to chew.1 The masticated leaves are stored in the buccal sulcus for about five hours during each chewing session and the saliva, and leaf extracts are usually swallowed.2
Recent improvement in air transportation to these areas has resulted in shipment of the plant to Europe and the United States.3 The growing habit of chewing khat has motivated an interest to further the knowledge on its active ingredients and pharmacological effects. The United Nations narcotics laboratory isolated an alkaloid (-) cathinone from young khat leaves. The (-) cathinone        is transformed into (+) pseudoephedrine during wilting of the leaves.3
Halback4 reviewed the clinical and pharmacological actions of khat and concluded that the effects were mainly due to the sympathomimetic ingredients of the plant. The psychotropic, cardiac, gastric and other 1,3,4 Chronic stomatitis has been observed in some khat users.1,2 This paper reports additional oral findings in two Yemeni nationals after prolonged use of khat.

Case Reports

Case 1

A 28-year-old Yemeni national presented to the Oral Medicine Clinic, College of Dentistry, King Saud University, Riyadh in April 1984. His chief complaint was painful intraoral sores which he had noticed in 1982 when he resumed chewing khat during a visit to his home country. He had used khat for 10 years prior to moving to Saudi Arabia wherein he stopped the habit. He was a smoker (20 sticks/day) but quit the habit one year before the onset of painful oral ulcers.

Oral examination showed a network of lacy white lines bilaterally on the buccal mucosa. At the center of the lacy network were deep ulcers covered with yellowish pseudomembrane about 1 cm at greatest dimension [Fig. 1]. The dorsum of the tongue showed multiple white round hyperkeratotic patches [Fig. 2]. Similar white patches were observed on the lateral and ventral aspects of the tongue.
Histological examination revealed hyperkeratinized stratified squamous epithelium, which is variably hyperplastic, atrophic and ulcerated. The epithelium has saw-tooth rete-bridge morphology with liquefaction degeneration of the basal cell layer [Fig.  3]. The underlying connective tissue contained dense chronic inflammatory cell infiltrate consisting predominantly of lymphocytes. The inflammatory cell infiltrate was rather diffuse and was not closely related to the epithelium. Aggregation of lymphocytes into follicles were observed within the inflammatory cell infiltrate. A mixed inflammatory cell infiltrate, consisting of polymorpho-nuclear leukocytes and lymphocytes, was seen in areas of the connective tissue that lacked epithelium. An eosinophilic band is seen immediately below the epithelium. Histopathological appearance was consistent with lichen planus or a lichenoid drug eruption. The patient was advised to stop smoking and was started on 0.1 % triamcinolone acetamide ointment mixed with equal parts of orabase paste applied topically four times daily.5 There was remarkable improvement after two weeks of treatment and complete resolution after five weeks.

Case 2

A 36-year-old male patient from Taiz, Northern Yemen attended the Oral Medicine Clinic at the College of Dentistry, King Saud University with a chief complaint of a burning mouth sensation of 2 weeks duration. The patient gave a history of rheumatoid arthritis, muscle pain and occasional paraesthesia in both arms and legs. He started chewing khat since the age often but stopped the habit two weeks before he experienced the burning sensation in the oral cavity. Clinical examination revealed bilateral buccal mucosal ulcerations surrounded by erythematous areas and white keratotic lines. The mucosal ulcerations extended from the commissures of the mouth to the retromolar region |Fig, 4|. White keratotic plaques were seen on the dorsal and ventral aspects of the tongue, the soft palate ana floor of the mouth; marginal gingiva was red and edematous. Histological evaluation of the specimen from the buccal mucosa showed relatively atrophic epithelium alternating with areas of complete lack of epithelium. Lymphocytes were evenly distributed with the atrophic epithelium. The epithelial connective tissue interface showed liquefaction degeneration and early vesicule formation. A band-like inflammatory infiltrate consisting predominantly of lymphocytes occupied the whole lamina propria [Fig. 5]. The patient was put on topical 0.1% triamcinolone acetamide in orabase paste applied four to five times daily. There was considerable improvement after four weeks of treatment, and patient was clear of any symptoms after a one-year follow up.

 
The active ingredients in khat identified to date include (-) cathinone, cathinine, cathidine, edulin and ephedrine.3 The most important of these active ingredients, (-) cathinone, is present mainly in young  leaves but  it   is   rapidly   transformed   to norpseudoephedrine during wilting of the leaves. Rapid transformation of the active ingredients might explain the special preference for the young leaves by khat users.
Stomatitis, esophagitis and gastritis have been reported as side effects of khat.4 Luqman and Danowski,2 observed generalized stomatitis among khat users, while Halbach2 reported esophagitis and gastritis in addition to stomatitis. Luqman and Danowski2 speculated that the concomitant smoking of tobacco, poor diet and vitamin deficiency may probably contribute to chronic irritation of the oral mucosa with subsequent superimposed infection. Hill and Gibson I observed low caries rate and inverse relationship between the periodontal pocket depth and the chewing side. They noticed some evidence of temporomandibular joint dysfunction and oral mucosa changes, such as hyperkeratosis and localized stomatitis.
The two cases presented in this report showed ex­tensive oral mucosal ulcerations with areas of hyperkeratosis. Histopathological features did not satisfy the criteria defined by Eisenberg and Krutchoff6 for diagnosing lichen planus. The inflammatory infiltrate observed in both cases were rather diffused and not closely related to the epithelium as in classical lichen planus. Lymphoid follicle deep in the lamina propria was noticed in one case.
Cigarette smoking7,8,9 and chrysotherapy for rheumatoid arthritis have been implicated as possible etiological agents of lichenoid tissue reaction.10,11 Although one of our patients gave a history of rheumatoid arthritis, he did not report the use of any medications. Neumann-jensen et al9 noticed a higher prevalence of plaque type of lichen planus in smokers compared to non-smokers. A history of smoking was given by one of our patients but he quit the habit one year prior to oral lichenoid eruptions.
Lichenoid drug reaction has been reported as a side effect of various drugs10,12 but never in conjunction with khat. Daffary et al,13 reported the occurrence of lichen planus-like lesions in the buccal mucosa of an Indian population that chewed betel nut. The oral mucosal lesions were observed adjacent lo the vestibular sulcus where the betel-tobacco was inserted.
The lichenoid tissue reaction is characterized by epithelial basal cell damage that is intimately associated with a massive infiltration of mononuclear cells in the upper connective tissue of the mucosa.10,14 The mechanism by which this cell damage occurs is not known. Recent experimental evidence gave support to a localized cell mediated immune response to an induced antigenic alteration in epithelial or epidermal cells of the mucosa or skin with the basal epithelial or epidermal cells perceived as foreign, because of the altered surface antigenicity.
Such alteration may occur in response to many different insults, such as physical trauma, action of chemicals, drugs, foods or microorganisms. The biochemical alterations of the epithelium and genetic factors may render an individual susceptible to such mucosal changes in response to any of the above stimulus. Many chemicals have been implicated in the etiology of lichenoid ulcerations. To our knowledge, this report is the first observation of a possible linkage between khat (Cathus edulis) and lichenoid ulcerations of the oral mucosa.