Official scientific distribution organ of Instituto Panvascular de Occidente
Metotrexato Induced Myelosuppression in Rheumatoid Arthritis
PDF Reporte de Caso (Spanish)

Keywords

Myelosuppression
Methotrexate
Rheumatoid arthritis

Categories

How to Cite

1.
Metotrexato Induced Myelosuppression in Rheumatoid Arthritis. Rev Med Clin [Internet]. 2024 Sep. 14 [cited 2024 Nov. 24];8(2):e28052408009. Available from: https://medicinaclinica.org/index.php/rmc/article/view/524

Abstract

Background: Patients with rheumatoid arthritis treated with methotrexate may have hematological damage, including myelosuppression, leukopenia, neutropenia, and megaloblastic anemia. The hematological toxicity causes up to 25\% of patients to discontinue treatment due to risk of mortality. Pancytopenia is among the toxicities of methotrexate and is difficult to prevent, as it can appear unexpectedly during therapy. Case report: A 70-year-old female patient with a diagnosis of rheumatoid arthritis, attended due to symptoms such as asthenia, adynamia, fever and pain in the oral mucosa. The blood count reports hemoglobin of 7.5 g/dL, leukocytes of 1700 µl, and platelets of 13,000/mm3. The patient is diagnosed with myelosuppression secondary to high doses of methotrexate, she is managed with blood products, hydration, folinic acid, granulocyte colony-stimulating factor rHu-G-CSF, and recombinant glycoprotein. She reports stable. Conclusions: Although methotrexate is effective in the treatment of many diseases, including rheumatoid arthritis, whether intentional or mistaken, especially in older adults, can cause serious side effects, including hematologic toxicity and increased risk of infections. The management of myelosuppression secondary to methotrexate has three main objectives, elimination of methotrexate from the bloodstream, therapy with folinic acid, and treatment of pancytopenia.

PDF Reporte de Caso (Spanish)

References

Cutolo M, Sulli A, Pizzorni C, Seriolo B, Straub RH. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis. 2001;60(8):729-735. doi:10.1136/ard.60.8.729.

Bedoui Y, Guillot X, Sélambarom J, Guiraud P, Giry C, et al. Methotrexate an Old Drug with New Tricks. Int. J. Mol. Sci.2019;20:5023. doi:10.3390/ijms20205023.

Lucas CJ, Dimmitt SB, Martin JH. Optimización de dosis bajas de metotrexato para la artritis reumatoide-A revisión. H. J Clin Pharmacol. 2019;85(10):2228-2234. doi:10.1111/bcp.14057.

Maksimovic V, Pavlovic-Popovic Z, Vukmirovic S, et al. Molecular mechanism of action and pharmacokinetic properties of methotrexate. Mol Biol Rep. 2020;47(6):4699-4708. doi:10.1007/s11033-020-05481-9.

Burmester, Gerd R., et al. "Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis in clinical practice: the Research in Active Rheumatoid Arthritis (ReAct) trial."Annals of the rheumatic diseases 66.6 (2007): 732-739.

Xu M, Wu S, Wang Y, et al. Association between high-dose methotrexate-induced toxicity and polymorphisms within methotrexate pathway genes in acute lymphoblastic leukemia. Front Pharmacol. 2022;13:1003812. doi:10.3389/fphar.2022.1003812.

Friedman B, Cronstein B. Methotrexate mechanism in treatment of rheumatoid arthritis. Joint Bone Spine. 2019;86(3):301-307. doi:10.1016/j.jbspin.2018.07.004.

Correal ML, Camplesi AC, Anai LA, Bertolo PHL, Vasconcelos RO, Santana ÁE. Toxicity of a methotrexate metronomic schedule in Wistar rats. Res Vet Sci. 2020;132:379-385. doi:10.1016/j.rvsc.2020.07.015.

Kaundal U, Khullar A, Leishangthem B, et al. The effect of methotrexate on neutrophil reactive oxygen species and CD177 expression in rheumatoid arthritis. Clin Exp Rheumatol. 2021;39(3):479-486. doi:10.55563/clinexprheumatol/4h5onh

Reiss AB, Teboul I, Kasselman L, Ahmed S, Carsons SE, De Leon J. Methotrexate effects on adenosine receptor expression in peripheral monocytes of persons with type 2 diabetes and cardiovascular disease. J Investig Med. 2022;70(6):1433-1437. doi:10.1136/jim-2022-002355.

Azadnasab R., Kalantar H., Khorsandi L., Kalantari H., Khodayar M.J. Epicatechin Ameliorative Effects on Methotrexate-Induced Hepatotoxicity in Mice. Hum. Exp. Toxicol. 2021;40:S603–S610. doi:10.1177/09603271211047924.

Kim Y.-J., Song M., Ryu J.-C. Mechanisms Underlying Methotrexate-Induced Pulmonary Toxicity. Expert Opin. Drug Saf. 2009;8:451–458. doi:10.1517/14740330903066734.

Letertre M.P.M., Munjoma N., Wolfer K., Pechlivanis A., McDonald J.A.K., Hardwick R.N., Cherrington N.J., Coen M., Nicholson J.K., Hoyles L., et al. A Two-Way Interaction between Methotrexate and the Gut Microbiota of Male Sprague–Dawley Rats. J. Proteome Res. 2020;19:3326–3339. doi:10.1021/acs.jproteome.0c00230.

Feinsilber D., Leoni R.J., Siripala D., Leuck J., Mears K.A. Evaluation, Identification, and Management of Acute Methotrexate Toxicity in High-Dose Methotrexate Administration in Hematologic Malignancies. Cureus. 2018;10:e2040. doi:10.7759/cureus.2040.

Ramalanjaona B., Hevroni G., Cham S., Page C., Salifu M.O., McFarlane S.I. Nephrotoxicity Associated with Low-Dose Methotrexate and Outpatient Parenteral Microbial Therapy: A Case Report, Review of the Literature and Pathophysiologic Insights. Am. J. Med. Case Rep. 2020;8:400–404. doi:10.12691/ajmcr-8-11-6.

Tornero Molina J, Ballina García FJ, Calvo Alén J, et al. Recommendations for the use of methotrexate in rheumatoid arthritis: up and down scaling of the dose and administration routes. Reumatol Clin. 2015;11(1):3-8. doi:10.1016/j.reuma.2014.02.012.

Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492–509. 10.1136/annrheumdis-2013-204573.

Lim AY, Gaffney K, Scott DG. Methotrexate-induced pancytopenia: serious and under-reported? Our experience of 25 cases in 5 years. Rheumatology. 2005;44(8):1051–1055.

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;41(3):427-432. doi:10.1590/2175-8239-JBN-2018-0095.

Prey S, Paul C. Effect of Folic or Folinic Acid Supplementation on Methotrexate-Associated Safety and Efficacy in Inflammatory Disease: A Systematic Review. Br. J. Dermatol. 2009;160:622–628. doi:10.1111/j.1365-2133.2008.08876.x.

Zhang Y, Liu P, Li Y, Zhang A. Exploration of metabolite signatures using high-throughput mass spectrometry coupled with multivariate data analysis. RSC Adv. 2017;7:6780-6787. doi:10.1039/C6RA27461G.

Dalrymple JM, Stamp LK, O'Donnell JL, Chapman PT, Zhang M, Barclay ML. Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 2008;58(11):3299-3308. doi:10.1002/Art.24034.

Chabner BA, Young RC. Threshold methotrexate concentration for in vivo inhibition of DNA synthesis in normal and tumorous target tissues. J Clin Invest. 1973;52(8):1804-1811. doi:10.1172/JCI107362.

Feinsilber D, Leoni RJ, Siripala D, Leuck J, Mears KA. Evaluation, Identification, and Management of Acute Methotrexate Toxicity in High-dose Methotrexate Administration in Hematologic Malignancies. Cureus. 2018;10(1):e2040. Published 2018 Jan 8. doi:10.7759/cureus.2040.

Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and Managing Toxicities of High-Dose Methotrexate. Oncologist. 2016;21(12):1471-1482. doi:10.1634/theoncologist.2015-0164.

Chiusolo P, Giammarco S, Bellesi S, et al. The role of MTHFR and RFC1 polymorphisms on toxicity and outcome of adult patients with hematological malignancies treated with high-dose methotrexate followed by leucovorin rescue. Cancer Chemother Pharmacol. 2012;69:691–696.

Al-Quteimat OM, Al-Badaineh MA. Methotrexate and trimethoprim-sulphamethoxazole: extremely serious and life-threatening combination. J Clin Pharm Ther. 2013;38(3):203-205. doi:10.1111/jcpt.12060.

Tornero Molina J, Ballina García FJ, Calvo Alén J, Caracuel Ruiz MA, et al. Recomendaciones para el uso del metotrexato en artritis reumatoide: incremento y reducción de dosis y vías de administración. Reumatología Clínica. 2015;11(1):3-8. https://doi.org/10.1016/j.reuma.2014.02.012.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright (c) 2024 Marisol Silva-Vera, Xochitl Viridiana Piña-Padilla, María de Jesús Jiménez-González, Raul Fernando Guerrero-Castañeda

Downloads

Download data is not yet available.