International Journal of Health Sciences and Research www.ijhsr.org ISSN: 2249-9571

Review Article

Plasma Cell Associated With Khat (Catha Edulis): A Brief Review

Sadeq Ali Al-Maweri1, Walid Ahmed Al-Soneidar2, Ghadah Al-Sufyani3, Saleem Abdulrab4, Ziyad kamal mohammad5, Amer Al Maqtari6

1Assistant Professor, Department of Oral Medicine and Diagnostic Sciences, AL-Farabi colleges, Riyadh, Saudi; Department of oral Medicine and Diagnosis, Faculty of Dentistry, Sana’a University, Yemen. 2Graduate Research Assistant, Department of Health Policy and Administration, Washington State University, Pullman, USA. 3General dental practitioner, Private Dental clinic, Sana’a, Yemen. 4Lecturer, Department of Restorative Dentistry, AL-Farabi Colleges, Riyadh, Saudi. 5Assistant Professor, Department of Prosthodontic & Conservative Dentistry, Faculty of Dentistry, Arab American University, Jenin, Palestine. 6General Dental Practitioner, Private Dental Center, Sana’a, Yemen.

Corresponding Author: Sadeq Ali Al-Maweri

Received: 28/05/2016 Revised: 15/06/2016 Accepted: 20/06/2016

ABSTRACT

Plasma cell stomatitis (PCS), an uncommon condition, is characterized by massive and dense infiltration of plasma cells into the connective tissue. The etiology of PCS is unclear, but this condition is believed to be an immunological reaction to certain allergens present in chewing gum, flavoring mint, dentifrices and cinnamon flavoring products. Recently, plasma cell stomatitis has also been reported among habitual khat chewers. Khat, a psychostimulant herb, is cultivated and habitually chewed by millions of people in East Africa and the Arabian Peninsula as well as by immigrants in the west. This article aims to briefly review the current literature of the association of PCS with Khat use and to highlight the treatment approaches for such cases. A review of the literature using PUBMED and Google Scholar revealed ten cases of PCS linked to khat use, most of which were identified in Yemen, where khat chewing is highly prevalent. Interestingly, however, two of the ten cases were also reported in western countries; one was about Somali immigrant in the Denmark and the other was a Yemeni immigrant in the US. Treatment of Khat related-PCS includes cessation of the habit and oral hygiene prophylaxis. The rise of global immigration may potentially increase the incidence of PCS and other khat-related oral lesions worldwide. Therefore, recognition of this habit and its implications on oral health should be emphasized.

Keywords: Plasma cell stomatitis, Khat use, association.

INTRODUCTION names such as oral plasma cell mucositis, (3) Plasma cell stomatitis/mucositis plasma cell , (4-7) allergic (PCS) is a rare benign condition gingivostomatitis,(8) atypical gingivostoma- characterized by prominent plasma cell titis, (9) idiopathic gingivostomatitis, (10) and infiltrate of the underlying lamina propria gingival plasmacytosis. (11) This condition is without evidence of malignancy, of chronic nature, and presents clinically as tuberculosis or candidal infection. (1,2) This marked mucosal erosions and erythema, rare condition is of unclear etiology and has especially on the gingiva with or without been reported in the literature under various ulceration. The lesions are usually

International Journal of Health Sciences & Research (www.ijhsr.org) 313 Vol.6; Issue: 7; July 2016 Sadeq Ali Al-Maweri et al. Plasma Cell Stomatitis Associated With Khat asymptomatic; however, patients may cardiovascular disorders, cytotoxic effects complain of pruritus, pain, burning on liver and kidneys, respiratory problems, sensation, discomfort, or in case of mental illnesses and gastrointestinal laryngeal involvement, dysphagia and/or disorders. (16) Oral conditions reportedly hoarseness. (2,3) Histopathological, PCS is associated with khat chewing include, but recognized mainly by a dense band like not limited to, keratotic white lesions, hairy plasmacytic infiltrate in the connective tongue, Xerostomia and periodontal tissue. (1) diseases. (18-21) Moreover, recent studies The exact etiology of PCS is still have reported PCS in association with khat unknown; it has been associated with many use. (3,14,15) allergens such as chewing gum, mint, and This habit is spreading beyond its toothpaste. (5,12,13) Recently, plasma cell original home in Yemen and Africa. Indeed mucositis has also been reported among the prevalence of khat use is raising globally habitual khat chewers. (3,14,15) Khat, also due to the worldwide immigration from East known as qat, Kat, and Miraa (Figure 1), is Africa and the Middle East countries. In an evergreen plant (Catha edulis) that Europe and North America, khat is sold in belongs to the Celastraceae family. (16) It is restaurants and grocery stores to East cultivated predominantly in East Africa and African and Middle Eastern. (16) In this the Arabian Peninsula, where millions of article, we briefly review the current local people habitually chew its fresh leaves literature regarding the association of PCS and twigs for their stimulating with Khat use, and also highlight the amphetamine-like effects. (16,17) Many treatment approaches for such cases. people from the region’s diaspora communities living in Europe, USA, and MATERIALS AND METHODS Australia also chew Khat regularly. Khat is The literature review was conducted usually chewed at social gathering (the so- using Medical Literature Analysis and called Khat session) that lasts for several Retrieval System Online (MEDLINE) hours per day; khat chewing is mainly a database and the search engine PubMed. male predominant habit, although the Moreover, Google Scholar was also used to number of women indulging this habit is on search for any relevant publications. We the rise. Typically, this habit involves used a combination of the following inserting and chewing a quantity of fresh keywords: khat and plasma cell stomatitis; khat leaves, forming bolus that is held in the Khat and plasma cell mucositis; khat and buccal sulcus against the cheek on one side plasma cell gingivitis; Qat and plasma cell of the mouth while swallowing its juice. (18) gingivitis; Qat and plasma cell mucositis; Long-term khat chewing has many Qat and plasma cell stomatitis. detrimental general health effects including

Table 1: Summary of the 10 PCS cases reported in the literature Reference Age Country* symptoms Location of lesions Treatment Marker and 30 UK Swelling Gingiva, mucobuccal sulcus, Discontinuation of khat use Krogdahl (15) cheek Rawal et al. (14) 40 USA Pain, swelling, bleeding upon Gingiva, buccal mucosa Discontinuation of khat use, brushing and eating analgesics, Oral prophylaxis Al-Akhali et al. 32 Yemen Pain, difficulty in Gingiva, , tongue, larynx Discontinuation of khat use (3) swallowing, hoarseness 20 Yemen pain Gingiva, palate Discontinuation of khat use 24 Yemen Pain, swelling Gingiva, Discontinuation of khat use 33 Yemen Soreness, swelling Gingiva, Discontinuation of khat use 24 Yemen none Gingiva, cheek Discontinuation of khat use 23 Yemen pain gingiva Discontinuation of khat use 29 Yemen Pain and swelling gingiva, lip, tongue, palate Discontinuation of khat use 22 Yemen Pain, hoarseness and Gingiva, tongue, buccal Discontinuation of khat use swallowing difficulty mucosa, lip, larynx *The country where the PMS cases were reported

International Journal of Health Sciences & Research (www.ijhsr.org) 314 Vol.6; Issue: 7; July 2016 Sadeq Ali Al-Maweri et al. Plasma Cell Stomatitis Associated With Khat

The search revealed 10 cases of plasma cell stomatitis/gingivitis (PCS) associated with khat use, reported in 3 studies (Table 1). Of these, one patient was a Somali immigrant in the Denmark, one Yemeni immigrant in the USA, and the other 8 cases were reported in Yemen.

Figure 1: Khat leaves

Figure 2: Plasma cell gingivitis affecting gingiva and tongue. A: Edematous and erythematous gingiva with some erosions. (B) Slight swelling and fibrin-covered ulceration on the lateral side of the tongue. This figure is adapted from Al-Akhali et al. (3)

DISCUSSION the other was a Somali immigrant in the PCS, an uncommon condition, is Denmark. All remaining cases reported benign plasma cell proliferative disorder of young adults in Yemen. All of these patients the upper aerodigestive tract. Although the were long-term regular khat chewers, who etiology of PCS is still unknown, some reported having the daily habit for several authors propose that the prominent presence years. In 2002, Marker and Krogdahl (15) of plasma cells suggests an allergic reaction reported the first case of Khat -related PCS that is associated with certain components in in a Somali immigrant in the Denmark. The toothpastes, mint pastel and food stuff. 30-year old male patient was referred to (4,12,13) Nevertheless, in some cases no agent department of oral and Maxillofacial could be identified and thus considered surgery by his dental surgeon for gingivitis- idiopathic. Interestingly, some recent reports like changes in the buccal gingiva that was have also linked PCS to Khat leaves. (3,14,15) refractory to the conventional periodontal A summary of the 10 khat-related treatment. The authors reported that lesions PCG cases reported in the literature is were mainly located on the left side of the presented in Table 1. The age of patients mouth, mainly on mandibular gingiva and was in the range of 20-40 years, with an buccal mucosa at the site of khat placement. average age of 30 years. All patients were The gingiva was described as intensely young males. Among the reported cases, erythematous and swollen with the presence one was a Yemeni immigrant in USA and of fibrin clot. The sulcus and the buccal

International Journal of Health Sciences & Research (www.ijhsr.org) 315 Vol.6; Issue: 7; July 2016 Sadeq Ali Al-Maweri et al. Plasma Cell Stomatitis Associated With Khat mucosa in the same side were also similarly PMS cases (cases associated with herbal affected. The histological analysis showed toothpaste and other allergens) were infiltration of polyclonal plasma cells. observed mostly in the anterior gingiva, Based on the history of habitual khat more frequently on the maxilla. By contrast, chewing as well as histopathological and in khat-related PCS, the changes were more clinical findings, the authors concluded that prominent on the facial posterior gingiva the final diagnosis was PCS with allergic involving the mucobuccal sulcus and the reaction. (15) adjacent buccal mucosa and to lesser extent, The second case reported a Yemeni some parts of tongue, palate and lip. This immigrant in the USA. The 40-year old can be explained by the direct contact with male presented with the complaint of pain, the allergen (Khat), which is usually placed swelling and extreme redness of the left on the mucobuccal sulcus, usually buccal gingiva. The clinical features and unilaterally, where it is held for several histopathological findings were identical to hours in direct contact with the gingiva and the above mentioned case. Likewise, the buccal mucosa. Moreover, in the above patient admitted that he always placed the mentioned cases, the cessation of khat khat in the left buccal mucosa. Therefore, chewing brought about remission or authors of this case also made a final significant improvement within days. This diagnosis of PCS. (14) indicates clearly that the erythema of the In 2014 Al-Khali and colleagues (3) gingiva and other parts of the mucosa was reported the largest series of khat-related mainly associated with khat use. It has been PCS. The authors reported 8 cases of PCS reported in the literature that PCS has slight among Yemeni young adults who presented male predominance of 1.2-1. (2) with different complaints to department of Interestingly, however, all khat-related PMS periodontology, Sana’a University. Similar cases were reported among males. This can to the previous two cases, Al-Akhali et al. be explained by the fact that khat habit is a reported the typical features of edematous predominantly men habit, rather than a and erythematous gingiva with velvety gender-related lesion. Moreover, compared surface accompanied with the involvement to females, Khat is more frequently of the adjacent buccal mucosa at the site of consumed and for longer hours among khat chewing. Interestingly, however, the males. (18) involvement of other parts of the mouth Khat chewing is associated with such as the tongue, palate, lips was evident several oral and dental adverse effects. It in most of these cases (Figure 2). Moreover, has been associated with white keratotic hoarseness, a sign of laryngeal involvement lesions, mucosal pigmentation, hairy that has rarely been reported in the tongue, poor oral hygiene, teeth literature, was noted in two cases. (3) discoloration and Xerostomia. (17,18,23,24) Some authors have categorized PCS Several studies have evaluated the into three subgroups: 1) caused by allergen, association between khat use and gingival 2) neoplastic, 3) unknown cause. (13,22) As and periodontal diseases; most studies found the changes and symptoms had developed a positive association (20,21,25) while a few after prolonged use of khat, PCS cases did not. (26) Khat contains several various discussed in this review seems to fall in the chemical constituents including first group. This is compatible to PMS psychoactive substances cathinone and caused by herbal toothpaste or other cathine, alkaloids, carbohydrates, tannic allergens. As noted above, all of the 10 acid, and other substances. (16) It is assumed patients were regular khat chewers, who that tannic acid is responsible for induced consumed khat for long time; and none of stomatitis among some of khat chewers. patients reported using any allergen known In addition to history taking as well to be related to PCS. Some of the reported as clinical and histological findings, the

International Journal of Health Sciences & Research (www.ijhsr.org) 316 Vol.6; Issue: 7; July 2016 Sadeq Ali Al-Maweri et al. Plasma Cell Stomatitis Associated With Khat diagnosis of PCS requires hematological of a case and review of the literature. analyses to exclude . Further Arch Dermatol. 1986; 122(11):1321-4. serological investigations are also needed to 2. Solomon LW, Wein RO, Rosenwald I, exclude similarly - appearing connective Laver N. Plasma cell mucositis of the tissue disorder like lupus erythematous. oral cavity: report of a case and review of the literature. Oral Surg Oral Med Other possible clinical differential diagnosis Oral Pathol Oral Radiol Endod. 2008; of PCS includes , mucous 106(6):853-60. membrane , , plaque- 3. Sultan Al-ak’hali M, Al-haddad KA, induced gingivitis, erythroplasia, sarcoidosis Al-hebshi NN. Oral plasma-cell (2) and Wegner’s granulomatosis mucositis exacerbated by qat chewing– Histopathological findings (plasma cell A case series. The Saudi Journal for infiltrate) should be differentiated from Dental Research. 2015; 6(1):60-6. other more serious disorders such as 4. Bali D, Gill S, Bali A. Plasma cell plasmacytoma and . (2,5) gingivitis - A rare case related to Management of PCS in general is Colocasia (arbi) leaves. Contemp Clin aimed to alleviate related symptoms. PCS is Dent. 2012; 3(Suppl 2):S182-4. 5. Macleod RI, Ellis JE. Plasma cell a benign condition with fairly well gingivitis related to the use of herbal prognosis, and progression to more serious toothpaste. Br Dent J. 1989; conditions such as plasma cell or 166(10):375-6. has never been reported in the 6. Patanwala A, Fisher EW, Chapple IL. literature. Generally, removal of the Plasma cell gingivitis affecting the offending allergen i.e. cessation of khat gingiva, palatal mucosa and laryngeal chewing habit in case of khat-related PCS cords. Perio. 2006; 3(2):123-8. results in improvement of the case with 7. Sollecito TP, Greenberg MS. Plasma possible complete resolution. Furthermore, cell gingivitis. Report of two cases. Oral removal of other local aggravating factors Surg Oral Med Oral Pathol. 1992; such as plaque and calculus is also crucial. 73(6):690-3. 8. Silverman S, Jr., Lozada F. An epilogue Topical anti-inflammatory medications such to plasma-cell gingivostomatitis as corticosteroids can be used in severe (allergic gingivostamtitis). Oral Surg cases to accelerate healing. Oral Med Oral Pathol. 1977; 43(2):211- 7. CONCLUSIONS 9. Owings JR, Jr. An atypical There is an association between gingivostomatitis: a report of four cases. Khat chewing and PCS. Given the fact that J Periodontol. 1969; 40(9):538-42. khat chewing habit is increasing worldwide 10. Perry HO. Idiopathic gingivostomatitis. with global immigration from countries of Dermatol Clin. 1987; 5(4):719-22. high use (East Africa and the Middle East), 11. Ferreiro JA, Egorshin EV, Olsen KD, it is becoming more likely that khat-related Banks PM, Weiland LH. plasmacytosis of the upper oral lesions including PCS will be seen aerodigestive tract. A clinicopathologic throughout the world. It is therefore study. Am J Surg Pathol. 1994; imperative that general dental practitioners, 18(10):1048-53. periodontists and oral medicine specialists, 12. Anil S. Plasma cell gingivitis among especially those in the new world should be herbal toothpaste users: a report of three aware of this habit and its association with cases. J Contemp Dent Pract. 2007; PCS and other oral complications. 8(4):60-6. 13. Kerr DA, McClatchey KD, Regezi JA. REFERENCES Idiopathic gingivostomatitis. , 1. White JW, Jr., Olsen KD, Banks PM. , gingivitis syndrome; atypical Plasma cell orificial mucositis. Report gingivostomatitis, plasma-cell gingivitis, plasmacytosis of gingiva.

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Oral Surg Oral Med Oral Pathol. 1971; for periodontitis: a cross-sectional 32(3):402-23. study. Int J Dent. 2013; 2013:317640. 14. Rawal SY, Rawal YB, Anderson KM, 21. Dhaifullah E, Al-Maweri SA, Al- Bland PS, Stein SH. Plasma cell Motareb F, Halboub E, Elkhatat E, gingivitis associated with khat chewing. Baroudi K, et al. Periodontal Health Perio. 2008; 5(5):21-8. Condition and Associated Factors 15. Marker P, Krogdahl A. Plasma cell among University Students, Yemen. J gingivitis apparently related to the use Clin Diagn Res. 2015; 9(12):ZC30-3. of khat: report of a case. Br Dent J. 22. Gargiulo AV, Ladone JA, Ladone PA, 2002; 192(6):311-3. Toto PD. Case report: plasma cell 16. Al-Hebshi NN, Skaug N. Khat (Catha gingivitis A. CDS Rev. 1995; 88(3):22- edulis)-an updated reviews. Addict Biol. 3. 2005; 10(4):299-307. 23. Al-Maweri SA, Al-Jamaei AA, Al- 17. Al-Maweri SA, Alaizari NA, Al- Sufyani GA, Tarakji B, Shugaa-Addin Sufyani GA. Oral mucosal lesions and B. Oral mucosal lesions in elderly their association with tobacco use and dental patients in Sana'a, Yemen. J Int qat chewing among Yemeni dental Soc Prev Community Dent. 2015; patients. J Clin Exp Dent. 2014; 5(Suppl 1):S12-9. 6(5):e460-6. 24. Yarom N, Epstein J, Levi H, Porat D, 18. Schmidt-Westhausen AM, Al Sanabani Kaufman E, Gorsky M. Oral J, Al-Sharabi AK. Prevalence of oral manifestations of habitual khat white lesions due to qat chewing among chewing: a case-control study. Oral women in Yemen. Oral Dis. 2014; Surg Oral Med Oral Pathol Oral Radiol 20(7):675-81. Endod. 2010; 109(6):e60-6. 19. Al-Maweri SA, Al-Sufyani G. OP144: 25. Ali AA. Qat habit in Yemen society: a Prevalence of , potentially causative factor for oral periodontal malignant lesions and oral habits among diseases. Int J Environ Res Public patients visiting dental school, Sana’a Health. 2007; 4(3):243-7. University. Oral Oncology. 2013; 26. Jorgensen E, Kaimenyi JT. The status of 49:S59. periodontal health and oral hygiene of 20. Al-Sharabi AK, Shuga-Aldin H, Miraa (catha edulis) chewers. East Afr Ghandour I, Al-Hebshi NN. Qat Med J. 1990; 67(8):585-90. chewing as an independent risk factor

How to cite this article: Al-Maweri SA, Al-Soneidar WA, Al-Sufyani Ghadah et al. Plasma cell stomatitis associated with Khat (Catha Edulis): a brief review. Int J Health Sci Res. 2016; 6(7):313-318.

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International Journal of Health Sciences & Research (www.ijhsr.org) 318 Vol.6; Issue: 7; July 2016