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Everolimus-Associated Stomatitis in a Patient Who Had Renal Transplant Yisi D Ji,1 Ali Aboalela,2 Alessandro Villa3

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Everolimus-Associated Stomatitis in a Patient Who Had Renal Transplant Yisi D Ji,1 Ali Aboalela,2 Alessandro Villa3 BMJ Case Reports: first published as 10.1136/bcr-2016-217513 on 19 October 2016. Downloaded from Novel treatment (new drug/intervention; established drug/procedure in new situation) CASE REPORT Everolimus-associated stomatitis in a patient who had renal transplant Yisi D Ji,1 Ali Aboalela,2 Alessandro Villa3 1Harvard School of Dental SUMMARY Everolimus can be used in renal allograft trans- Medicine, Boston, Everolimus is used as an immunosuppressant in renal plantations.3 This requires new approaches to Massachusetts, USA 910 2Ministry of National Guard allograft transplant rejection and in metastatic breast address everolimus-associated stomatitis. Here, Health Affairs, Riyadh, cancer treatment. One side effect of everolimus is we describe a useful management strategy for Saudi Arabia stomatitis, referred to as mammalian target of symptomatic treatment and prophylaxis of mIAS in 3 Department of Oral Medicine rapamycin inhibitor-associated stomatitis. This side effect a patient who had renal transplant. and Dentistry, Brigham and can affect treatment course and contribute to Women’s Hospital, Boston, Massachusetts, USA discontinuation of therapy or dose reduction, previously CASE PRESENTATION reported in the treatment of metastatic breast cancer. A 48-year-old female was referred to the Division of Correspondence to Here, we present a case of everolimus-associated Oral Medicine and Dentistry at Brigham and Yisi D Ji, [email protected]. stomatitis with a novel management method with ’ ‘ ’ edu Women s Hospital for painful oral swelling . The intralesional triamcinolone that allows for continuous patient presented with persistent pain in the lower Accepted 5 October 2016 course of everolimus. mandibular region and tongue for 5 days. Medications at time of the Oral Medicine consult included everolimus 0.75 mg two times per day, metoprolol 25 mg two times per day, methylpredni- BACKGROUND solone 4 mg once daily, valganciclovir 900 mg two Everolimus is a mammalian target of rapamycin times per day and ergocalciferol 50 000 units once (mTOR) inhibitor derived from sirolimus, origin- weekly. Her medical history was significant for ally produced by Streptomyces hygroscopicus.1 hypertension, anaemia, hyperlipidaemia and end- Everolimus reduces the activity of mTOR by stage renal disease secondary to polycystic kidney binding to FK-binding protein, thereby preventing disease. The patient underwent a renal transplant cell cycle progression and proliferation.1 from a living unrelated donor 364 days prior. The Everolimus is an FDA-approved agent for advanced donor was cytomegalovirus (CMV)-positive and the breast cancer and pancreatic neuroendocrine recipient was CMV-negative. Throughout the entire tumours.2 It is also used as an immunosuppressant postoperative course, the patient was leucopenic. http://casereports.bmj.com/ in renal allograft transplant rejection.3 Preclinical Prophylactic valganciclovir was discontinued models show that everolimus prevents acute rejec- 6 months after transplantation to improve the leuco- tion of kidney transplants and reduces rejection.4 cyte count. Forty-five days after discontinuing val- Vascular remodelling in transplant allografts is sug- ganciclovir, the patient developed CMV viraemia gested to be part of graft dysfunction.4 Everolimus and CMV colitis. The patient was switched to evero- prevents this process from occurring by inhibiting limus 0.75 mg two times per day from tacrolimus smooth muscle cell proliferation and reducing 4.5 mg two times per day that the patient had been intimal thickening process.4 on since the transplant, because of potential 11 12 One of the side effect of everolimus, and other anti-CMV effects of everolimus. The patient mTOR inhibitors, is oral stomatitis.5 mTOR developed discomfort on the right mandibular area on 25 September 2021 by guest. Protected copyright. inhibitor-associated stomatitis (mIAS) can signifi- for 42 days after starting everolimus. At the time of cantly affect the treatment course and may contrib- the visit, everolimus was therapeutic at 6.1 ng/mL ute to discontinuation of therapy.6 mIAS has been reported to range from 43% to 70%.578Other side effects of everolimus include nasopharyngitis, shortness of breath and acne-like lesions.7 de Oliveira et al6 describe a case series revealing five patients required discontinuation of treatment due to stomatitis and five patients required dose reduc- tions of everolimus secondary to stomatitis in the course of their cancer treatment. Reduction in dose or discontinuation of everolimus may compromise optimal outcomes, such as graft survival in patients To cite: Ji YD, Aboalela A, who had renal transplants.9 Everolimus is used in Villa A. BMJ Case Rep Published online: [please renal transplant to prevent graft rejection and is include Day Month Year] associated with a lower risk of cytomegalovirus doi:10.1136/bcr-2016- infections compared to rapamycin or sirolimus, a 217513 common concern in patients who had transplants.9 Figure 1 Everolimus-associated stomatitis. Ji YD, et al. BMJ Case Rep 2016. doi:10.1136/bcr-2016-217513 1 2 Novel treatment (new drug/intervention; established drug/procedure in new situation) Table 1 Cases of mIAS secondary to everolimus use that describes management strategies Author (year) Type of article Disease mTOR Dosage Intervention Duration Discussion Kalogirou et al13 Case series Renal cell carcinoma and breast cancer Everolimus 5 mg qd Magic Mouthwash* four times daily 3–15 days mIAS healed in 3–15 days. (2014) 10 mg qd Nicolatou-Galitis Case series HER2+ breast cancer Everolimus 10 mg qd Dexamethasone solution 0.5 mg/mL and 1–2 weeks Ulcers healed within 1–2 weeks of either et al15 (2013) miconazole 2% gel (1–2 weeks), four discontinuing everolimus or treatment with patients discontinued everolimus dexamethasone solution and miconazole gel de Oliveira et al6 Case series Cervical chordoma, leiomyosarcoma, Everolimus 10 mg Topical anaesthetics, Magic Mouthwash†, Variable Median time to onset of ulcers was 10 days. One of (2011) osteosarcoma, spindle cell sarcoma, Ridaforolimus 12.5 mg clobetasol gel 0.05%, dexamethasone 17 patients discontinued therapy due to mIAS. Five of liposarcoma, merkel cell carcinoma, 40 mg 0.1 mg/mL, triamcinolone paste, 17 had dose reductions due to mIAS. thyroid carcinoma, Waldenstrom intralesional triamcinolone, systemic macroglobulinaemia prednisone (1 mg/kg for 7 days) Ferté et al17 (2011) Chart review Non-small-cell lung cancer, small-cell lung Everolimus Ranged from Sodium bicarbonate-based mouthwash, Variable Patients with prior chemotherapy or receiving higher cancer or breast cancer 2.5 mg qd to oral fluconazole doses of everolimus had higher rates of ulcers and for 10 mg qd, or longer durations. Ten per cent of patients required 20 mg qw to dose delay because of mIAS and 9% required dose 30 mg qw reduction due to mIAS. Empirical treatment with sodium bicarbonate-based mouthwash, oral fluconazole, did not show improvement in mIAS within 5 days after onset. Sahin et al18 Retrospective Patients who had renal transplant Sirolimus NA NA NA Reducing calcineurin inhibitor-based therapy, (2011) chart review switched from calcineurin-based therapies Everolimus switching to sirolimus or everolimus, was beneficial to sirolimus or everolimus for GFR Vermeulen et al19 Case report Severe stomatitis in a patient who had Everolimus Local anaesthetic Not Oral local anaesthetics used but no effect on (2010) cardiac transplant after switching to specified aphthous ulcers; required discontinuing everolimus everolimus secondary to mIAS, requiring conversion to cyclosporine and azathioprine Ji YD, De Simone et al20 Prospective 40 patients who had renal transplants Everolimus 0.75 mg BID NA NA Everolimus can be used in place of a calcineurin (2009) inhibitor-based therapy in patients with liver allograft et al without a decrease in efficacy. et al21 BMJ Case Rep Ram (2008) Case report Patients who had renal transplant on Everolimus 0.75 mg BID Sirolimus switched to everolimus Patient developed aphthous ulcers on sirolimus and sirolimus switched to everolimus then switched to everolimus. Aphthous ulcers subsequently resolved. Peterson et al22 Literature NA Everolimus NA Preventative steroid mouth rinses NA mIAS can affect the delivery of mTOR inhibitor (2016) review Temsirolimus (NCT02069093) therapy. 2016. doi:10.1136/bcr-2016-217513 Ridaforolimus Sirolimus Boers-Doets et al14 Literature NA mTOR NA NA NA mIAS are frequent side effects in patients with cancer (2013) review inhibitors with genes playing a potential role. *Magic Mouthwash (lidocaine gel 2%×30 g, doxycycline suspension 50 mg/5 mL×60 mL and sucralfate oral suspension 1000 mg/5 mL dissolved in sodium chloride 0.9%×2000 mL).13 † Magic Mouthwash (lidocaine, aluminium hydroxide, magnesium hydroxide, dimethicone suspension, diphenhydramine, equal parts). BID, two times a day; GFR, glomerular filtration rate; HER2, human estrogen receptor 2; mIAS, mTOR inhibitor-associated stomatitis; mTOR, mammalian target of rapamycin; qd, four times a day; qw, every week. BMJ Case Reports: first published as 10.1136/bcr-2016-217513 on 19 October 2016. Downloaded from from Downloaded 2016. October 19 on 10.1136/bcr-2016-217513 as published first Reports: Case BMJ http://casereports.bmj.com/ on 25 September 2021 by guest. Protected by copyright. by Protected guest. by 2021 September 25 on BMJ Case Reports: first published as 10.1136/bcr-2016-217513 on 19 October 2016. Downloaded from Novel treatment (new drug/intervention; established
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