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Oral Presentation of Chronic Hyperplastic Candidiasis in Patient under Imatinib Mesylate: A Rare Case

Article · April 2016

DOI: 10.17354/cr/2016/217

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IJSS Case Reports & Reviews | April 2016 | Vol 2 | Issue 11 17

Oral Presentation of Chronic Hyperplastic Candidiasis in Patient under Imatinib Mesylate: A Rare Case

Vishwanath Pattar1, Zameera Nalaband2, Anjana Bagewadi3

1Post Graduate Student, Department of Oral Medicine and Radiology, KLE Vishwanath Katti Institute of Dental Sciences, Belagavi, Karnataka, India, 2Professor, Department of Oral Medicine and Radiology, KLE Vishwanath Katti Institute of Dental Sciences, Belagavi, Karnataka, India, 3Head and

Professor, Department of Oral Medicine and Radiology, KLE Vishwanath Katti Institute of Dental Sciences, Belagavi, Karnataka, India

Candida albicans is the major human pathogen among Candida species. It is a commensal yeast of the oral, gastrointestinal, and vaginal mucosa in healthy individuals. Tie genus Candida has about 154 species, and difgerent species show a difgerent level of resistance to antifungal drugs and have a high degree of phenotypic similarity. Oropharyngeal candidiasis is the most common infection in oral cavity both pre- and post-treatment of cancer. Immunocompromised state in a cancer patient induces candidal species which get activated as a pathogen. It is found that in certain high-risk groups antifungal prophylaxis reduces the incidence and severity of infections. Tiis case report discusses the

• ccurrence of hyperplastic candidiasis in the patient under treatment by a chemotherapeutic agent imatinib mesylate for gastric tumor. We

have discussed the probable cause for oral candidiasis in patients under imatinib mesylate and treatment advised for the oral hyperplastic candidiasis. Keywords: Candida, Candidiasis, Chemotherapy, Imatinib mesylate

Some cases have been reported about the lesion in the oral cavity such as painful erosions with lichenoid reactions in patients under imatinib mesylate.5 Till date, there are no case reports about occurrence of oral candidiasis in patients who are under treatment of imatinib mesylate. The most common form of oral candidiasis in cancer patients are pseudomembranous and erythematous type of candidiasis while the hyperplastic type of candidiasis is rarely reported.6 Herein, we report a rare case of oral hyperplastic candidiasis in a patient under the treatment of malignant gastric tumor with imatinib mesylate.

CASE REPORT

A 48-year-old female patient reported to our Department of Oral Medicine and Radiology with a chief complaint of pain in the gums in both right and left side of lower jaw. The pain was moderate, burning type, intermituent, and aggravates while chewing food or drinking water relieves on taking

• rest. The patient gave medical history of malignant tumor

in the hypogastric region on left side for which she had undergone surgery 4 months back. The patient was on the medication, glivac 400 mg tablets (imatinib mesylate 400 mg, Novartis Pharma AG, Swit{erland) daily since 4 months. On general examination subconjunctival pallorness, pallorness

• f the nail bed were seen. On extra oral examination,

INTRODUCTION

Imatinib mesylate is a chemotherapeutic drug, which acts as a tyrosine kinase inhibitor and is used in the treatment of acute lymphoblastic leukemia, chronic eosinophilic leukemia, gastrointestinal stromal tumor, myelodysplastic/myeloproliferative neoplasm, systemic mastocytosis, etc.1,2 Short-term toxicity of the imatinib mesylate in 1-10% includes pancytopenia, febrile neutropenia, and fmushing. Imatinib mesylate inhibition of c-kit and platelet-derived growth factor receptors (PDGF-R), which plays role in normal immune responses, causing altered immune function.2 It has been reported that there is a signifjcant hypogammaglobulinemia in patients treated with imatinib mesylate.3 Fungal infections in patients under certain other chemotherapeutic drugs occurs due to suppressed oral/mucosal immunity, salivary gland dysfunction causing xerostomia and alteration in oral fmora.4

Case Report

DOI: 10.17354/cr/2016/217 Corresponding Author:

• Dr. Vishwanath Pattar, Department of Oral Medicine and Radiology, KLE Vishwanath Katti Institute of Dental Sciences, Nehru Nagar,

Belagavi - 590 010, Karnataka, India. E-mail: dr.vishwanthpattar@gmail.com Access this article online www.ijsscr.com Month of Submission : 02-2016 Month of Peer Review : 03-2016 Month of Acceptance : 03-2016 Month of Publishing : 04-2016

Pattar, et al.: A Rare Case of Oral Presentation of Chronic Hyperplastic Candidiasis in Patient under Imatinib Mesylate IJSS Case Reports & Reviews | April 2016 | Vol 2 | Issue 11 18

submandibular lymph nodes were palpable on both right and left side 3 in number on the right side and 1 in number

• n the left side. Lymph nodes were of dimension 1 cm each

in left side and 1.5 cm on right side. Lymph nodes were fjrm in consistency, tender on palpation, mobile. On intraoral examination white hyperkeratotic patch was seen on gingiva extending from distal of 43 to mesial of 47 and anteriorly in relation to 32, 31, 41, 42 and on left side in relation to 34, 35 and lingual to 47, 48 of the mandibular jaw (Figures 1 and 2). Superiorly hyperkeratotic patch extending from atuached gingival to the buccal vestibular region inferoirly. Surface

• ver the hyperkeratotic area was rough and borders were
• irregular. Gingiva surrounding the hyperkeratotic area was

erythematous and tender on palpation. Hyperkeratotic area was non-scrapable on application of pressure with gauze piece at its entire extent. There was the presence of white coating on the tongue. Superfjcial layer was forcibly scraped ofg with blunt end

• f the BP blade, and the pathological evaluation was

advised wherein Candida albicans were isolated. On the basis of history, clinical and pathological fjndings, a fjnal diagnosis of chronic hyperplastic candidiasis was given. Antifungal treatment with clotrimazole 1% mouth paint and chlorhexidine mouthwash of 0.12% were started and followed up after 2 weeks, and there was 30% decrease in the size of the lesion (Figures 3 and 4). Further follow-up of patient was not possible in the event of death of the patient.

DISCUSSION

Mutations of c-kit proto-oncogene are reported in 85%, and mutations of PDGF-Rα chain are reported in 35% of gastointestinal tumors.7 BCR-ABL tyrosine kinase is the product of Philadelphia chromosome, which is a causative factor for chronic myelogenous leukemia.8 Imatinib is an inhibitor of the receptor tyrosine kinases for PDGF and stem cell factor (SCF), c-kit, and inhibits PDGF and SCF-mediated cellular events and thereby acts as anti-tumor drug.2 Therefore, imatinib mesylate is used either as the

Figure 1: Pre-treatment image showing hyperkeratotic area on the buccal aspect of 43-47 Figure 2: Pre-treatment image showing hyperkeratotic area on the labial aspect

• f 43 on right side to 35 on left side

Figure 3: Post-treatment image with reduced hyperkeratotic area on buccal aspect of 43-47 Figure 4: Post-treatment image with reduced hyperkeratotic area on labial aspect 43-35 region

Pattar, et al.: A Rare Case of Oral Presentation of Chronic Hyperplastic Candidiasis in Patient under Imatinib Mesylate IJSS Case Reports & Reviews | April 2016 | Vol 2 | Issue 11 19

fjrst line of treatment or as an adjuvant in the treatment of gastrointestinal tumors.9 The most common side efgect of other chemotherapeutic drugs like methotrexate, cyclophosphamide related to

• ral cavity is oral mucositis. Mucositis provides favorable

conditions for the development of oral candidiasis. Candida, commensal yeast of the digestive tract, is capable

• f colonizing mucositis lesions and infecting the oral
• mucosa. Overall, 60-90% of mucositis lesions are infected

by Candida.10 For candidiasis to occur particularly in chemotherapeutic patients, there has to be altered local resistance to the infection (e.g., Xerostomia), compromised immune function (e.g., altered functions of infmammatory cells), and generalized debilitation of the patient (e.g., malnutrition and malabsorption).11 Oral lesions associated with imatinib mesylate reported are painful erosions associated with lichenoid reactions.5 The cause for oral candidiasis in patients under treatment with imatinib mesylate is unknown. However, it can be hypothesized that as there will be altered immune function, hypogammaglobulinemia leading to immunocompromised state in patients with imatinib mesylate drug therapy along with the associated poor oral hygiene can aggravate the normal commensal Candida to colonize leading to oral candidiasis, as was reported in the present case (Figure 5). Cases have been reported in which there was reactivation of hepatitis B virus after the therapy with imatinib mesylate.12 In our case, candidiasis was treated with clotrimazole 1% mouth paint, local application 5 times daily. Other treatment options for oral candidiasis include nystatin (available as a suspension of 100,000 U/mL (4-6 mL q.i.d.) or as fmavored 200,000 U pastilles (one or two 4-5 times daily) for 7-14 days).12 Chlorhexidine mouthwash 0.12% used in 1:1 dilution with water, for 3 times a day. However, most important intervention is to maintain proper

• ral hygiene, as in most of the cases poor oral hygiene is

the main inducing factor for the occurrence of candidiasis.

CONCLUSION

Oral candidiasis is an avoidable complication in chemotherapeutic patients. Educating the patients about the oral hygiene maintenance by referring them to dentist is a piece of advice needed to be provided by the oncologist. As the chances of occurrence of oral candidiasis are high, regular oral hygiene maintenance, regular referral to the dentist is important as to improve the quality of life of the patient.

REFERENCES

1. Available from: htup://www.cancer.gov. National Cancer Institute. Available from: htup://www.cancer.gov/about-cancer/treatment/ drugs/imatinibmesylate. [Last accessed on 2014 Sep 17; Cited on 2015 Jul 15]. 2. Mughal TI, Schrieber A. Principal long-term adverse efgects of imatinib in patients with chronic myeloid leukemia in chronic

• phase. Biologics 2010;4:315-23.

3. Santachiara R, Mafgei R, Martinelli S, Arcari A, Piacentini F, Trabacchi E, et al. Development of hypogammaglobulinemia in patients treated with imatinib for chronic myeloid leukemia or gastrointestinal stromal tumor. Haematologica 2008;93:1252-5. 4. Akpan A, Morgan R. Oral candidiasis. Postgrad Med J 2002;78:455-9. 5. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schifger C, Gambacorti-Passerini C, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002;346:645-52. 6. Lalla RV, Latortue MC, Hong CH, Ariyawardana A, D’Amato-Palumbo S, Fischer DJ, et al. A systematic review of

• ral fungal infections in patients receiving cancer therapy. Support

Care Cancer 2010;18:985-92. 7. Dematueo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: A randomised, double-blind, placebo-controlled trial. Lancet 2009;373:1097-104. 8. Remesh A. Toxicities of anticancer drugs and its management. Int J Basic Clin Pharmacol 2012;1:2-12. 9. Byung WK, Lee SJ. Chronic myeloid leukemia patient manifesting fatal hepatitis B virus reactivation during treatment with imatinib rescued by liver transplantation: Case report and literature review. Int J Hematol 2009;90:383-7.

• 10. Borg C, Terme M, Taïeb J, Ménard C, Flament C, Robert C, et al.

Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor efgects. J Clin Invest 2004;114:379-88.

• 11. Burket LW. Textbook of Oral Medicine. 11th ed. Hamilton: BC

Decker Inc.; 2008.

• 12. Williams D, Lewis M. Pathogenesis and treatment of oral
• candidosis. J Oral Microbiol 2011;3.

Figure 5: Pathogenesis of oral candidiasis How to cite this article: Pattar V, Nalaband Z, Bagewadi A. Oral Presentation

• f Chronic Hyperplastic Candidiasis in Patient under Imatinib Mesylate: A Rare
• Case. IJSS Case Reports & Reviews 2016;2(11):17-19.

Source of Support: Nil, Confmict of Interest: None declared.

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