Development of pancytopenia after single low-dose methotrexate therapy in patients with chronic kidney disease: a review of the literature

Yıl 2020, Cilt: 2 Sayı: 3, 83 - 90, 29.07.2020

İbrahim Akdağ Alparslan Ersoy

https://doi.org/10.46310/tjim.766086

Cited By: 2

Öz

Methotrexate (MTX) is widely used in the treatment of both rheumatoid arthritis (RA) and psoriatic arthritis (PA) with a side effect of pancytopenia. However, very few cases of severe pancytopenia caused by low-dose MTX therapy have been described in chronic kidney disease. Pancytopenia occurred after using a single dose of MTX in three patients with chronic kidney dysfunction. While one patient died due to sepsis and multiple organ failure, the others recovered. The severity of MTX-inducedpancytopenia in our cases was likely related to the underlyingkidney disease. These cases suggest that uremic patients may develop severe fatal bone marrow toxicity even with a single dose of MTX. Therefore, close blood count monitoring after MTX treatment in this population would be beneficial.

Anahtar Kelimeler

Chronic kidney disease, methotrexate, psoriatic arthritis, rheumatoid arthritis, pancytopenia

Kaynakça

• 1. O'Dell JR. Methotrexate use in rheumatoid arthritis. Rheum Dis Clin North Am. 1997 Nov;23(4):779-96. doi: 10.1016/s0889-857x(05)70360-4.
• 2. Haustein UF, Rytter M. Methotrexate in psoriasis: 26 years' experience with low-dose long-term treatment. J Eur Acad Dermatol Venereol. 2000 Sep;14(5):382-8. doi: 10.1046/j.1468-3083.2000.00058.x.
• 3. Lucas CJ, Dimmitt SB, Martin JH. Optimising low-dose methotrexate for rheumatoid arthritis-A review. Br J Clin Pharmacol. 2019 Oct;85(10):2228-2234. doi: 10.1111/bcp.14057.
• 4. Hirshberg B, Muszkat M, Schlesinger O, Rubinow A. Safety of low dose methotrexate in elderly patients with rheumatoid arthritis. Postgrad Med J. 2000 Dec;76(902):787-9. doi: 10.1136/pmj.76.902.787.
• 5. Basile C, Montanaro A, Semeraro A. Should low-dose methotrexate therapy be prescribed to dialysis patients? Nephrol Dial Transplant. 2002 Mar;17(3):530-1. doi: 10.1093/ndt/17.3.530.
• 6. Kremer JM. Major side effects of low-dose methotrexate. In: O'Dell JR, Romain PL, eds. UpToDate (last update: Apr 06, 2020).
• 7. Weinblatt ME, Fraser P. Elevated mean corpuscular volume as a predictor of hematologic toxicity due to methotrexate therapy. Arthritis Rheum. 1989 Dec;32(12):1592-6. doi: 10.1002/anr.1780321214.
• 8. Kivity S, Zafrir Y, Loebstein R, Pauzner R, Mouallem M, Mayan H. Clinical characteristics and risk factors for low dose methotrexate toxicity: a cohort of 28 patients. Autoimmun Rev. 2014 Nov;13(11):1109-13. doi: 10.1016/j.autrev.2014.08.027.
• 9. Kuitunen T, Malmström J, Palva E, Pettersson T. Pancytopenia induced by low-dose methotrexate. A study of the cases reported to the Finnish Adverse Drug Reaction Register From 1991 to 1999. Scand J Rheumatol. 2005 May-Jun;34(3):238-41. doi: 10.1080/03009740510018570.
• 10. Serraj K, Federici L, Maloisel F, Alt M, Andrès E. [Pancytopenia related to low-dose methotrexate: study of five cases and review of the literature]. Rev Med Interne. 2007 Sep;28(9):584-8. doi: 10.1016/j.revmed.2007.03.007.
• 11. Attar SM. Adverse effects of low dose methotrexate in rheumatoid arthritis patients. A hospital-based study. Saudi Med J. 2010 Aug;31(8):909-15.
• 12. Gutierrez-Ureña S, Molina JF, García CO, Cuéllar ML, Espinoza LR. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum. 1996 Feb;39(2):272-6. doi: 10.1002/art.1780390214.
• 13. Ohosone Y, Okano Y, Kameda H, Hama N, Matsumura M, Nojima T, Nakamura K, Kuwana M, Ogasawara T, Hirakata M, Yoshida T, Mimori T, Akizuki M, Ikeda Y. Toxicity of low-dose methotrexate in rheumatoid arthritis--clinical characteristics in patients with MTX-induced pancytopenia and interstitial pneumonitis. Ryumachi. 1997 Feb;37(1):16-23.
• 14. Nakazaki S, Murayama T, Katoh S. Cytopenia associated with low dose pulse methotrexate in the treatment of rheumatoid arthritis. Ryumachi. 2001 Dec;41(6):929-37.
• 15. Sosin M, Handa S. Low dose methotrexate and bone marrow suppression. BMJ. 2003 Feb 1;326(7383):266-7. doi: 10.1136/bmj.326.7383.266.
• 16. Calvo-Romero JM. Severe pancytopenia associated with low-dose methotrexate therapy for rheumatoid arthritis. Ann Pharmacother. 2001 Dec;35(12):1575-7. doi: 10.1345/aph.1A052.
• 17. Preet Singh Y, Aggarwal A, Misra R, Agarwal V. Low-dose methotrexate-induced pancytopenia. Clin Rheumatol. 2007 Jan;26(1):84-7. doi: 10.1007/s10067-006-0301-7.
• 18. Ellman MH, Ginsberg D. Low-dose methotrexate and severe neutropenia in patients undergoing renal dialysis. Arthritis Rheum. 1990 Jul;33(7):1060-1. doi: 10.1002/art.1780330724.
• 19. Grove ML, Hassell AB, Hay EM, Shadforth MF. Adverse reactions to disease-modifying anti-rheumatic drugs in clinical practice. QJM. 2001 Jun;94(6):309-19. doi: 10.1093/qjmed/94.6.309.
• 20. Songsiridej N, Furst DE. Methotrexate--the rapidly acting drug. Baillieres Clin Rheumatol. 1990 Dec;4(3):575-93. doi: 10.1016/s0950-3579(05)80008-1.
• 21. Ulrich CM, Yasui Y, Storb R, Schubert MM, Wagner JL, Bigler J, Ariail KS, Keener CL, Li S, Liu H, Farin FM, Potter JD. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood. 2001 Jul 1;98(1):231-4. doi: 10.1182/blood.v98.1.231.
• 22. Berkun Y, Levartovsky D, Rubinow A, Orbach H, Aamar S, Grenader T, Abou Atta I, Mevorach D, Friedman G, Ben-Yehuda A. Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene. Ann Rheum Dis. 2004 Oct;63(10):1227-31. doi: 10.1136/ard.2003.016337.
• 23. Chess JA, Scholey G, Mikhail AI. Neutropenia associated with the use of low-dose methotrexate in a peritoneal dialysis patient. Nephrol Dial Transplant. 2004 Aug;19(8):2158-9. doi: 10.1093/ndt/gfh357.
• 24. Lim AY, Gaffney K, Scott DG. Methotrexate-induced pancytopenia: serious and under-reported? Our experience of 25 cases in 5 years. Rheumatology (Oxford). 2005 Aug;44(8):1051-5. doi: 10.1093/rheumatology/keh685.
• 25. Ajmani S, Preet Singh Y, Prasad S, Chowdhury A, Aggarwal A, Lawrence A, Misra R, Mishra R, Agarwal V. Methotrexate-induced pancytopenia: a case series of 46 patients. Int J Rheum Dis. 2017 Jul;20(7):846-851. doi: 10.1111/1756-185X.13004.
• 26. Kremer JM, Petrillo GF, Hamilton RA. Pharmacokinetics and renal function in patients with rheumatoid arthritis receiving a standard dose of oral weekly methotrexate: association with significant decreases in creatinine clearance and renal clearance of the drug after 6 months of therapy. J Rheumatol. 1995 Jan;22(1):38-40.
• 27. Chatham WW, Morgan SL, Alarcón GS. Renal failure: a risk factor for methotrexate toxicity. Arthritis Rheum. 2000 May;43(5):1185-6. doi: 10.1002/1529-0131(200005)43:5<1185::AID-ANR30>3.0.CO;2-V.
• 28. Sun CY, Lin HC, Chen YC, Tsai CR, Wu MS. Leukemoid Reaction After Methotrexate-Induced Pancytopenia in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis. Chang Gung Med J. Sep-Oct 2006;29(5):513-7.
• 29. Aristizabal-Alzate A, Nieto-Rios JF, Ocampo-Kohn C, Serna-Higuita LM, Bello-Marquez DC, Zuluaga-Valencia GA. Successful multiple-exchange peritoneal dialysis in a patient with severe hematological toxicity by methotrexate: case report and literature review. J Bras Nefrol. 2019 Jul-Sep;41(3):427-432. doi: 10.1590/2175-8239-JBN-2018-0095.
• 30. Boulanger H, Launay-Vacher V, Hierniaux P, Fau JB, Deray G. Severe methotrexate intoxication in a haemodialysis patient treated for rheumatoid arthritis. Nephrol Dial Transplant. 2001 May;16(5):1087. doi: 10.1093/ndt/16.5.1087.
• 31. Liu H, Liu F, Zhang M, Yan W, Sang H. Combined acute interstitial pneumonitis and pancytopenia induced by low-dose methotrexate in a hemodialysis patient treated for bullous pemphigoid. An Bras Dermatol. 2015 May-Jun;90(3 Suppl 1):43-5. doi: 10.1590/abd1806-4841.20153692.
• 32. Liu WC, Chen HC, Chen JS. Clinical dilemma over low-dose methotrexate therapy in dialysis patients: a case report and review of literature. Iran J Kidney Dis. 2014 Jan;8(1):81-4.
• 33. Diskin CJ, Stokes TJ, Dansby LM, Radcliff L, Carter TB. Removal of methotrexate by peritoneal dialysis and hemodialysis in a single patient with end-stage renal disease. Am J Med Sci. 2006 Sep;332(3):156-8. doi.org/10.1097/00000441-200609000-00013.
• 34. Boey O, Van Hooland S, Woestenburg A, Van der Niepen P, Verbeelen D. Methotrexate should not be used for patients with end-stage kidney disease. Acta Clin Belg. 2006 Jul-Aug;61(4):166-9. doi: 10.1179/acb.2006.028.
• 35. Yang CP, Kuo MC, Guh JY, Chen HC. Pancytopenia after low dose methotrexate therapy in a hemodialysis patient: case report and review of literature. Ren Fail. 2006;28(1):95-7. doi: 10.1080/08860220500461328.
• 36. Mima A, Nagahara D, Tansho K. Methotrexate induced pneumatosis intestinalis under hemodialysis patient. Hemodial Int. 2017 Jan;21(1):E9-E12. doi: 10.1111/hdi.12459.
• 37. Seneschal J, Héliot-Hostein I, Taieb A. Pancytopenia induced by low-dose methotrexate in a haemodialysis patient treated for bullous pemphigoid. J Eur Acad Dermatol Venereol. 2007 Sep;21(8):1135-6. doi: 10.1111/j.1468-3083.2006.02122.x.
• 38. Willner N, Storch S, Tadmor T, Schiff E. Almost a tragedy: severe methotrexate toxicity in a hemodialysis patient treated for ectopic pregnancy. Eur J Clin Pharmacol. 2014 Mar;70(3):261-3. doi: 10.1007/s00228-013-1608-3.
• 39. Bruyn GA, Velthuysen E, Joosten P, Houtman PM. Pancytopenia related eosinophilia in rheumatoid arthritis: a specific methotrexate phenomenon? J Rheumatol. 1995 Jul;22(7):1373-6.
• 40. Nakamura M, Sakemi T, Nagasawa K. Severe pancytopenia caused by a single administration of low dose methotrexate in a patient undergoing hemodialysis. J Rheumatol. 1999 Jun;26(6):1424-5.
• 41. Cheung KK, Chow KM, Szeto CC, Tai MH, Kwan BC, Li PK. Fatal pancytopenia in a hemodialysis patient after treatment with low-dose methotrexate. J Clin Rheumatol. 2009 Jun;15(4):177-80. doi: 10.1097/RHU.0b013e3181a61f2d.
• 42. Flynn KN, Johnson MS, Brink WC, Smith DL. Pancytopenia, mucositis, and hepatotoxicity after intralesional methotrexate injection in a patient treated with peritoneal dialysis. Am J Health Syst Pharm. 2012 Apr 1;69(7):578-82. doi: 10.2146/ajhp110252.
• 43. Hoekstra M, van Ede AE, Haagsma CJ, van de Laar MA, Huizinga TW, Kruijsen MW, Laan RF. Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis. Ann Rheum Dis. 2003 May;62(5):423-6. doi: 10.1136/ard.62.5.423.
• 44. Bressolle F, Bologna C, Kinowski JM, Sany J, Combe B. Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients. Ann Rheum Dis. 1998 Feb;57(2):110-3. doi: 10.1136/ard.57.2.110.
• 45. Ahmad S, Shen FH, Bleyer WA. Methotrexate-induced renal failure and ineffectiveness of peritoneal dialysis. Arch Intern Med. 1978 Jul;138(7):1146-7.
• 46. Seyffart G. Poison index: The treatment of acute intoxication. Lengerich: Pabst Science Publishers; 1997;449-51.
• 47. Widemann BC, Balis FM, Kempf-Bielack B, Bielack S, Pratt CB, Ferrari S, Bacci G, Craft AW, Adamson PC. High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma. Cancer. 2004 May 15;100(10):2222-32. doi: 10.1002/cncr.20255.
• 48. Wall SM, Johansen MJ, Molony DA, DuBose TD Jr, Jaffe N, Madden T. Effective clearance of methotrexate using high-flux hemodialysis membranes. Am J Kidney Dis. 1996 Dec;28(6):846-54. doi: 10.1016/s0272-6386(96)90384-4.
• 49. Murashima M, Adamski J, Milone MC, Shaw L, Tsai DE, Bloom RD. Methotrexate clearance by high-flux hemodialysis and peritoneal dialysis: a case report. Am J Kidney Dis. 2009 May;53(5):871-4. doi: 10.1053/j.ajkd.2009.01.016.
• 50. Saland JM, Leavey PJ, Bash RO, Hansch E, Arbus GS, Quigley R. Effective removal of methotrexate by high-flux hemodialysis. Pediatr Nephrol. 2002 Oct;17(10):825-9. doi: 10.1007/s00467-002-0946-7.
• 51. Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, et all. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017 Jun;76(6):960-977. doi: 10.1136/annrheumdis-2016-210715.
• 52. Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat Rev. 1995 Jan;21(1):33-64. doi: 10.1016/0305-7372(95)90010-1.
• 53. Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR, Paulus HE, Mudano A, Pisu M, Elkins-Melton M, Outman R, Allison JJ, et all; American College of Rheumatology. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762‐784. doi:10.1002/art.23721.