Oral Plasma-Cell Mucositis Exacerbated by Qat Chewing – a Case Series Mohammed Sultan Al-Ak’Hali, Khaled Abdulsalam Al-Haddad, Nezar Noor Al-Hebshi

Oral plasma-cell mucositis exacerbated by qat chewing – A case series Mohammed Sultan Al-Ak’hali, Khaled Abdulsalam Al-Haddad, Nezar Noor Al-Hebshi

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Mohammed Sultan Al-Ak’hali, Khaled Abdulsalam Al-Haddad, Nezar Noor Al-Hebshi. Oral plasma- cell mucositis exacerbated by qat chewing – A case series. The Saudi Journal for Dental Research, Elsevier, 2015, 6 (1), pp.60-66. 10.1016/j.sjdr.2014.05.001. hal-03168668

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CASE REPORT Oral plasma-cell mucositis exacerbated by qat chewing – A case series

Mohammed Sultan Al-ak’hali a, Khaled Abdulsalam Al-haddad b, Nezar Noor Al-hebshi c,d,* a Department of Periodontology, Faculty of Dentistry, Sana’a University, Sana’a, Yemen b Department of Orthodontic and Pediatric Dentistry, Faculty of Dentistry, Sana’a University, Sana’a, Yemen c Department of Preventive Dentistry (Periodontology), Faculty of Dentistry, Jazan University, Saudi Arabia d Substance Abuse Research Center (SARC), Jazan University, Saudi Arabia

Received 10 March 2014; revised 30 April 2014; accepted 9 May 2014

KEYWORDS Abstract Plasma-cell mucositis (PCM) is a rare idiopathic condition that affects the mucus Catha edulis; membrane at one or more of the body orifices. We hereby present eight cases of oral PCM Khat; associated with qat chewing. The patients (all males, 20–33 years old) presented with chronic Plasma cell gingivitis; painful inflammatory mucosal lesions involving different sites of the oral cavity, particularly the Plasma cell mucositis; gingiva. An erythematous and swollen gingiva with velvety surface was a typical feature. Areas Qat of epithelial sloughing and/or erosions were also noticed. In seven patients, the lesion also affected the tongue, palate, lip and/or buccal mucosa. Hoarseness was observed in some of the patients suggesting laryngeal involvement. The symptoms correlated with patterns of qat chewing. Histological examination revealed dense infiltration of lamina propria by benign plasma cells. Lymphocytosis and/or elevated IgG titer were the main laboratory findings. This provides further evidence that PCM can at least be exacerbated by the habit of qat chewing. ª 2014 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

1. Introduction

Plasma-cell mucositis (PCM), or more accurately plasma-cell orificial mucositis, is a rare idiopathic condition that affects the mucus membrane at one or more of the body orifices, and is characterized by dense infiltration of lamina propria by * Corresponding author at: Faculty of Dentistry, Jazan University, plasma cells without evidence of malignancy, fungal infection P.O. Box: 114, Jazan, Saudi Arabia. Tel.: +966 565288886. 1 2 E-mail address: [email protected] (N.N. Al-hebshi). or tuberculosis. PCM was first described by Zoon et al. as Peer review under responsibility of King Saud University. involving the glans penis, but was reported later in other parts of the body. Cases affecting the oral cavity have been described using alternative terms, such as atypical gingivostomatitis,3,4 idiopathic gingivostomatitis,5 plasma cell-gingivitis,6–9 gingival Production and hosting by Elsevier plasmacytosis10–12 and plasma-cell cheilitis.13,14 Because 2352-0035 ª 2014 King Saud University. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.sjdr.2014.05.001

Please cite this article in press as: Al-ak’hali MS et al. Oral plasma-cell mucositis exacerbated by qat chewing – A case series, The Saudi Journal for Dental Research (2014), http://dx.doi.org/10.1016/j.sjdr.2014.05.001 2 M.S. Al-ak’hali et al. reported cases have been clinically and histopathologically and hoarseness. According to the patient, the severity of symp- indistinguishable from each other, all plasma-cell infiltrates of toms correlated with qat chewing; however, he had started the the aerodigestive tract have been grouped under the name habit 4 years prior to the onset of the condition. The patient orificial plasma-cell mucositis.1 reported previous unsuccessful treatment with nistatin. On The condition is chronic in nature. Clinically, the affected clinical examination, the free and attached gingiva as well as mucosa appears intensely erythematous with velvety, and the palate appeared edematous, slightly erythematous, and sometimes cobblestone or nodular, surface. Symptoms include shining with areas of erosion; the chewing side was more pain, dysphagia and hoarseness.15 PCM of the oral cavity has severely involved and showed gingival recession buccal to the been thought to represent allergic reactions to ingredients in premolars and molars (Fig. 1A). No periodontal involvement chewing gums or dentifrices.6,7,11,16–18 Spices, such as chili was detected clinically or radiographically. The lateral side of pepper and cinnamon, as well as environmental substances the tongue was swollen with bleeding or fibrin-covered ulcer- have also been suggested as allergens among patients with oral ations (Fig. 1B). Hoarseness observed was suggestive of laryn- PCM.11,19,20 However, extensive allergy testing have been geal involvement. inconclusive and many of the reported cases have been of Laboratory investigations showed the patient had slight unknown cause and thus considered idiopathic.9 lymphocytosis (51%) and elevated IgG titer, and was positive Qat, erroneously spelled khat, is the common name for for anti-nuclear antibodies (ANA). Microscopic examination Catha edulis, an evergreen plant endemic to Southwest of Ara- of a gingival biopsy revealed subepithelial infiltration with bia and Eastern Africa, where people habitually chew its fresh plasma cells (Fig. 2) without any cellular atypia which was leaves and twigs for their amphetamine-like stimulating consistent with PCM. Candidal infection was ruled out by effects.21 Typically, a person chews a quantity of 100–200 mg periodic acid-Schiff (PAS) staining. fresh qat material, forming a bolus that is kept against the cheek on one side of the mouth, while swallowing the juice. 2.2. Case 2 A chewing session, which is usually in the form of a social 21 gathering, lasts between 4 and 10 h. Information about the A 20-year-old male presented with chronically inflamed palate potential medical and oral adverse health effects of the habit and gingiva. The patient reported the symptoms were aggra- 21,22 can be found in a number of recent reviews. Its influence vated by qat chewing which he had been indulging in for on periodontal health in particular has been a controversial 10 years. However, as with the first case, he had had the symp- issue, with reports of both beneficial and detrimental effects. toms for only 6 years. Clinically, the patient had generalized 23 According to a recent model developed by Al-Sharabi et al., gingival inflammation extending from the free gingival margin qat chewing in the short run may be compatible with periodon- to the mucogingival junction in both the maxillary and man- tal health through its cleansing action and by inducing favor- dibular arches with diffuse whitening/epithelial sloughing. able bacterial community shifts; however, in the long run it The inflammation was more pronounced in the lower arch par- can contribute to more attachment loss and gingival recession ticularly on the chewing left side, (Fig. 3A). There was due to chronic mechanical trauma. profound gingival bleeding on probing despite the presence Two cases of PCM, confined to the gingiva and thus called of little plaque; however, no attachment loss was detected. plasma cell gingivitis (PCG), have been linked in the literature The palate was also involved and had a cobblestone appear- to the habitual chewing of qat leaves; one was a Yemeni ance. The lesions significantly improved after qat-chewing 24 immigrant in USA and the other a Somali immigrant in cessation for two weeks although gingival redness and slight 25 UK. In this paper, we present a series of 8 Yemeni patients swelling could still be observed (Fig. 3B). with qat-associated oral PCM. The patient had slight lymphocytosis (49%) and elevated IgG titer. Histologically, there was marked vasodilatation 2. Clinical presentations and an intense inflammatory infiltrate in the connective tissue dominated by plasma cells without any cellular atypia or can- Over a period of 1 year, eight systemically-healthy male didal hyphae which was consistent with PCM. patients, aged 20–33 years, presented at our private clinic and the Department of Periodontology at the Faculty of 2.3. Case 3 Dentistry, Sana’a University, with a history of chronic painful inflammatory mucosal lesions involving different sites of the This was a 24-year-old male patient complaining of reddish oral cavity, particularly the gingiva. All patients were habitual painful gingiva and swollen lip occurring immediately after qat chewers, and did not respond to conventional periodontal qat chewing. The patient had been chewing qat for 6 years therapy. The clinical and laboratory findings of the patients but the lesions had only started before 2 years. Clinically, the are summarized in Table 1. Written informed consent was gingiva appeared erythematous and slightly swollen with a vel- obtained from the patients for publication of this case series vety surface and areas of epithelial sloughing and erosions; a and any accompanying images. Copies of the written consent sharp demarcation at the mucogingival junction was also are available for review from the Editor of this journal. noted (Fig. 4A & B). There was no evidence of bone loss. Extra-oral examination revealed palpable and painful subman- 2.1. Case 1 dibular lymph nodes bilaterally. Laboratory investigations revealed the patient had slight A 32-year-old male patient presented with a 6-year history of lymphocytosis (44%) and elevated IgG, and was ANA posi- painful inflammation of the mucosa involving the gingiva, tive. Histological findings were consistent with PCM as palate, lips and tongue along with difficulty in swallowing described above.

Table 1 Clinical and laboratory ﬁndings for the eight cases. Case Age Sites involved IgG elevated ANA Lymphocytosis ESR elevated Gingiva Lips Tongue Palate 132+++++++ À 220+À +++ À + À 324++À ++ ++ À 433++À + ÀÀÀÀ 524+ÀÀ À À À ++ 623++À ++ À + À 729+++++ À ++ 822+++++ À ++

Figure 1 (A) Edematous and erythematous gingiva with velvety surface and areas of erosions; gingival recession is also evident. (B) The lateral side of the tongue showing slight swelling and ﬁbrin-covered ulceration.

ing for 16 years. Clinical examination revealed soft, edematous and erythematous gingiva with glistening surface. The signs were more pronounced on the chewing side; the lip showed slight swelling (cheilitis) with bleeding cracks (Fig. 5). No periodontal involvement was evident clinically and on radio- graphs. Submandibular lymph nodes bilaterally were palpable and tender. The patient had unremarkable hematological ﬁndings. Microscopically, there was again a dense inﬁltration of lamina propria by benign plasma cell with no evidence of malignancy or fungal infection.

2.5. Case 5

A 24-year-old male presented with gum inflammation that was Figure 2 Histological section from a gingival biopsy showing exacerbated by qat chewing. The patient had commenced the parakeratinized stratified epithelium and dense infiltration of habit 10 years ago; however the lesions had started to appear lamina propria with benign plasma cells (H and E; original only 7 years later. Clinically, diffuse gingival swelling and ery- magnification 400·). thema with glistering surface and spots of epithelial sloughing and erosion were observed; the chewing side and lower anterior region were more severely involved (Fig. 6A & B). The 2.4. Case 4 cheek on the chewing side was also inflamed, while the palate was not involved. Blood analysis showed marked lymphocyto- A 33-year-old male patient presented with a 5-year history of sis (76%), increased erythrocytes sedimentation rate (55 mm/ sore, swollen lips and gums. The severity of symptoms corre- h) and elevated IgG titer. Microscopic findings were consistent lated with patterns of qat chewing which he had been practic- with PCM.

Figure 3 (A) Swollen and erythematous gingiva with diffuse epithelial sloughing (whitening). (B) Partial clinical improvement after 2 weeks of qat cessation.

Figure 4 Edematous and velvety red gingiva with areas of erosions and epithelial sloughing; clear demarcation at the mucogingival junction. (A) Lower anterior mandible. (B) Upper left maxilla; lip involvement is evident.

2.6. Case 6

This was a 23-year-old male patient complaining of reddish, painful gingiva and swollen lip in association with qat chewing. The patient reported a 10-year history for the habit but a 2-year history for the lesion. The changes comprised diffuse swelling and erythema of the gingiva with erosions in some areas. Both sides of the mouth were involved although inflammation was more pronounced on the chewing side. Abnormal laboratory findings included marked lymphocytosis (74%) and elevated IgG titer. Hematoxylin-eosin (H & E) stained sections obtained from gingival biopsies revealed presence of eroded epithelium with elongated rete pegs, and dense subepithelial infiltrate of non-malignant plasma cells but also including a few lymphocytes.

Figure 5 Soft gingival swelling and erythema involving the 2.7. Case 7 anterior mandible and maxilla and extending posteriorly to both the chewing and non-chewing sides. A bleeding crack on the lip is A 29-year-old male patient presented with a 5-year history of also evident. sore, swollen lips and gums. Again the patient reported the

Figure 6 Diffuse intense gingival erythema with slight edema and with small areas of epithelial sloughing and erosion; sharp demarcation is evident at the mucogingival junction. The chewing side (A) is more severely involved than the non-chewing side (B).

lesions were exacerbated by qat chewing which he had been chewing of qat leaves.24,25 One was a Yemeni immigrant in indulging in for about 10 years. Clinical examination revealed USA and the other a Somali immigrant in UK. This is, there- soft, edematous and erythematous gingiva, particularly on the fore, the first report of multiple cases of oral PCM associated lower anterior segment and posterior upper segment on the with qat use from Yemen, where the habit is endemic. chewing side. No clinical attachment loss was detected. The The age of the cases in this series was in the range of 20– tongue and palate were also involved. Cessation of qat chew- 33 years, which is much lower than the average age of ing for 1 week resulted in considerable improvement. 56.6 years documented for PCM.15 However, the previously Laboratory investigation showed lymphocytosis, increased reported UK and USA cases were also younger (30 and ESR (28 mms/h), and elevated IgG titer. Microscopic exami- 40 years old, respectively) suggesting that qat-associated nation of gingival biopsies revealed a dense subepithelial cellu- PCM typically affects young adults. Interestingly, the age of lar infiltrate composed largely of mature plasma cells which PCM cases linked to the use of herbal tooth pastes in previous did not show anaplasia or prominent nucleoli. No candidal reports also falls within the same range.16,26 All patients in this hyphae could be found on PAS staining. series as well as the previous two reports were males. This, however, should not be interpreted as a higher susceptibility 2.8. Case 8 to the disease in males; rather, it can be better explained by the fact that qat-chewing is predominantly a male habit.21 Nevertheless, a slight male predilection (1.2:1) has been A 22-year-old male presented with a 2-month history of pain- reported for PCM.15 ful gingival lesion, difficulty swallowing and hoarseness. The An edematous and erythematous gingiva with velvety sur- patient had been chewing qat for 6 years, and indicated that face and a sharp demarcation at the mucogingival junction the habit was worsening his condition. On clinical examina- was a typical feature, which is consistent with previous reports. tion, the chewing side showed a soft, edematous and reddish Characteristically, however, areas of whitening, epithelial gingiva with glistening surface (Fig. 7A), while the non-chew- sloughing and erosion were frequently observed, which is sel- ing side appeared healthy (Fig. 7B). The lip, tongue, palate, dom mentioned in the literature. Involvement of other parts and buccal mucosa on the chewing side showed similar of the mouth was also evident, which is in contrast to the changes to those of the gingiva. Submandibular lymph nodes two previously reported cases in which the lesions were con- were tender to palpation bilaterally. Hoarseness was suggestive fined to the gingiva.24,25 Hoarseness was observed in some of of laryngeal involvement. The lesions showed complete remis- the cases suggesting laryngeal involvement which has been sion after 14 days of qat chewing cessation. rarely reported in association with PCM.19 Submandibular Hematological evaluation revealed slight lymphocytosis lymph nodes were palpable and tender in 3 patients, a manifes- (50%), and elevated IgG titer and ESR (13 mm/h). Histologi- tation that has not been previously reported except in a single cal examination demonstrated dense sub-epithelial infiltrate of recent report, in which the lymph node enlargement was found non-malignant plasma cells. to be reactive.15 A number of diseases that bear resemblance to PCM clini- 3. Discussion cally or/and histopathologically had to be excluded. Clinically, mucous membrane pemphigoid, erosive lichen planus, candidi- PCM is generally accepted as an idiopathic condition, asis, contact mucositis, chronic glaucomatous sarcoidosis, sys- although allergy to food or herbal toothpaste ingredients has temic lupus erythematosus and Wegener’s granulomatosis been proposed as a possible etiology.1,9 So far, two cases of were included in the differential diagnosis. They were, how- oral PCM have been linked in the literature to the habitual ever, ruled out upon histological examination since plasma cell

Figure 7 (A) Gingiva on the chewing side showing velvety erythema and edema. (B) The non-chewing side showing normal and healthy gingiva.

infiltrates are not a feature of any of them. Absence of fungal in the oral mucosa. It can also be argued that the lack of com- infection was further confirmed by performing PAS staining. plete clinical improvement on cessation may have simply been Solitary extramedullary plasmacytoma (SEP), which is a due to the short period the patients were willing to cease the malignancy of plasma cell with infiltrates similar to those of habit, and that a complete discontinuation would eventually PCM, was histologically excluded by the absence of any cellu- result in complete remission of the disease. lar atypia. Testing for clonality, which is usually performed to The main limitation of this case series is that follow up of exclude SEP, was not possible due to lack of resources. patients was not adequate. Failure to do so was largely because The results of laboratory investigations of our patients are, most of them were referred from other provinces/cities and however, difficult to interpret in view of the existing literature were thus unwilling to stay for long in the capital, especially since no remarkable laboratory findings have been reported for after knowing the condition was benign. It was, therefore, any of the previously described oral PCM cases, including the not possible to monitor the effect of qat cessation on the long two qat-associated cases. Lymphocytosis was noted in seven of term, or to confirm cessation status before attempting treat- the patients, in the absence of other blood cell count abnor- ment with topical or systemic cortisone. malities suggestive of malignancy. IgG was elevated in six of them while IgE level was within the normal range. Lympho- 4. Conclusion cytes could be precursors of the plasma cell infiltrating the mucosa, which are in turn producing large amounts of poly- This series does substantiate the evidence on the association clonal IgG that are drained via lymphatic system to the blood. between qat chewing and oral PCM. Since the habit has spread In fact, plasma cells in immunohistological sections of PCM 15,27 with immigrants to many countries, it is becoming more likely have indeed been found to be producers of IgG. However, that general dental practitioners and specialists anywhere in further investigation is definitely required to have a better the world may encounter cases of qat-associated oral PCM. understanding of the link between PCM and these laboratory They should in turn be aware about of this association to be findings. able to diagnose and manage the condition. All cases had a history of association between the severity of symptoms and qat chewing, suggesting that oral PCM can Conflict of interest be induced by the habit. However, all patients reported a chewing history that is much longer than that of the disease. In addition, while cessation of the habit resulted in clinical None declared. improvement, complete remission was only seen in one case. Furthermore, oral PCM does not seem to occur at higher rates References in areas were qat chewing is highly prevalent. These findings favor the view that oral PCM is idiopathic and that qat chew- 1. White Jr JW, Olsen KD, Banks PM. Plasma cell orificial ing is likely to be an exacerbating factor rather than a causative mucositis. Report of a case and review of the literature. Arch one. Dermatol 1986;122(11):1321–4. On the other hand, it can still be proposed that the diag- 2. Zoon JJ. Differential diagnosis between chronic circumscribed benign plasmacellular balanitis and Queyrat’s erythroplasia. Ned nosed oral PCM cases represent an allergic reaction to qat Tijdschr Geneeskd 1952;96(38):2349–53. chewing similar to that documented for chewing gums and her- 3. Owings Jr JR. An atypical gingivostomatitis: a report of four bal dentifrices. Developing the lesions years after commencing cases. J Periodontol 1969;40(9):538–42. the habit may be explained by the possibility that a sort of 4. Perry HO, Deffner NF, Sheridan PJ. Atypical gingivostomatitis. allergen build up is required for an allergic reaction to occur Nineteen cases. Arch Dermatol 1973;107(6):872–8.

5. Perry HO. Idiopathic gingivostomatitis. Dermatol Clin 17. Kerr DA, McClatchey KD, Regezi JA. Allergic gingivostomatitis 1987;5(4):719–22. (due to gum chewing). J Periodontol 1971;42(11):709–12. 6. Lubow RM, Cooley RL, Hartman KS, McDaniel RK. Plasma-cell 18. Silverman Jr S, Lozada F. An epilogue to plasma-cell gingivosto- gingivitis. Report of a case. J Periodontol 1984;55(4):235–41. matitis (allergic gingivostamtitis). Oral Surg Oral Med Oral Pathol 7. Macleod RI, Ellis JE. Plasma cell gingivitis related to the use of 1977;43(2):211–7. herbal toothpaste. Br Dent J 1989;166(10):375–6. 19. Patanwala A, Fisher EW, Chapple ILC. Plasma cell gingivitis 8. Palmer RM, Eveson JW. Plasma-cell gingivitis. Oral Surg Oral affecting the gingiva, palatal mucosa and laryngeal cords. Med Oral Pathol 1981;51(2):187–9. Periodontal Pract Today 2006;3(2):123–8. 9. Sollecito TP, Greenberg MS. Plasma cell gingivitis. Report of two 20. Serio FG, Siegel MA, Slade BE. Plasma cell gingivitis of unusual cases. Oral Surg Oral Med Oral Pathol 1992;73(6):690–3. origin. A case report. J Periodontol 1991;62(6):390–3. 10. Ferreiro JA, Egorshin EV, Olsen KD, Banks PM, Weiland LH. 21. Al-Hebshi NN, Skaug N. Khat (Catha edulis)-an updated review. Mucous membrane plasmacytosis of the upper aerodigestive tract. Addict Biol 2005 Dec;10(4):299–307. A clinicopathologic study. Am J Surg Pathol 1994;18(10): 22. Thomas S, Williams T. Khat (Catha edulis): a systematic review of 1048–53. evidence and literature pertaining to its harms to UK users and 11. Poswillo D. Plasmacytosis of the gingiva. Br J Oral Surg society. Drug Sci Policy Law 2013;1:1–25. 1968;5(3):194–202. 23. Al-Sharabi AK, Shuga-Aldin H, Ghandour I, Al-Hebshi NN. Qat 12. Timms MS, Sloan P. Association of supraglottic and gingival chewing as an independent risk factor for periodontitis: a cross- idiopathic plasmacytosis. Oral Surg Oral Med Oral Pathol sectional study. Int J Dent 2013;2013:3594978 serial on the 1991;71(4):451–3. Internet. Available from: http://www.ncbi.nlm.nih.gov/entrez/ 13. Baughman RD, Berger P, Pringle WM. Plasma cell cheilitis. Arch query.fcgi?cmd=Retrieve&db = PubMed&dopt=Citation&list_ Dermatol 1974;110(5):725–6. uids=23509461. 14. Tamaki K, Osada A, Tsukamoto K, Ohtake N, Furue M. 24. Marker P, Krogdahl A. Plasma cell gingivitis apparently related to Treatment of plasma cell cheilitis with griseofulvin. J Am Acad the use of khat: report of a case. Br Dent J 2002;192(6):311–3. Dermatol 1994;30(5 Pt 1):789–90. 25. Rawal SY, Rawal YB, Anderson KM, Bland PS, Stein SH. Plasma 15. Solomon LW, Wein RO, Rosenwald I, Laver N. Plasma cell cell gingivitis associated with khat chewing. Periodontal Pract mucositis of the oral cavity: report of a case and review of the Today 2008;5(1):21–8. literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 26. Lamdari N, Pradhan S. Plasma cell gingivitis: a case report. 2008 Dec;106(6):853–60. JNMA J Nepal Med Assoc 2012;52(186):85–7. 16. Anil S. Plasma cell gingivitis among herbal toothpaste users: a 27. Aiba S, Tagami H. Immunoglobulin-producing cells in plasma cell report of three cases. J Contemp Dent Pract 2007;8(4):60–6. oriﬁcial mucositis. J Cutan Pathol 1989;16(4):207–10.