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Fatal intoxication caused by conventional-dose methotrexate in an elderly patient with end-stage renal disease: A cautionary case report.

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Τίτλος: Fatal intoxication caused by conventional-dose methotrexate in an elderly patient with end-stage renal disease: A cautionary case report.
Συγγραφείς: He Q; Department of Emergency, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China., Huang X; Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Πηγή: Medicine [Medicine (Baltimore)] 2026 Aug 21; Vol. 105 (34), pp. e50331.
Τύπος έκδοσης: Journal Article; Case Reports
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 2985248R Publication Model: Print Cited Medium: Internet ISSN: 1536-5964 (Electronic) Linking ISSN: 00257974 NLM ISO Abbreviation: Medicine (Baltimore) Subsets: MEDLINE
Imprint Name(s): Original Publication: Hagerstown, Md : Lippincott Williams & Wilkins
Ιατρικοί όροι (MeSH): Methotrexate*/administration & dosage , Methotrexate*/adverse effects , Methotrexate*/poisoning , Methotrexate*/blood , Kidney Failure, Chronic*/complications , Antirheumatic Agents*/administration & dosage , Antirheumatic Agents*/adverse effects, Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/complications ; Multiple Organ Failure/chemically induced ; Humans ; Male ; Aged ; Fatal Outcome
Περίληψη: Rationale: Methotrexate (MTX) is a first-line agent for rheumatoid arthritis, and impaired renal excretion drastically elevates the risk of fatal drug accumulation. End-stage renal disease (ESRD) patients face an extreme toxicity risk even under conventional low-dose MTX, yet related fatal cases remain underreported. This case highlights critical clinical warnings for rheumatologists and emergency physicians.
Patient Concerns: A 71-year-old male with a 5-year history of rheumatoid arthritis and 1-year untreated chronic kidney disease stage 5 received weekly 10 mg subcutaneous MTX for 3 consecutive weeks without folic acid supplementation or regular laboratory monitoring. One day after his latest injection, he developed persistent nausea, vomiting, extensive oral ulcers, a skin rash, and drowsiness.
Diagnoses: Severe MTX intoxication complicated by profound bone marrow suppression, septic shock, and multiple organ dysfunction syndrome. Persistently elevated serum MTX confirmed impaired renal drug clearance in ESRD.
Interventions: Immediate MTX discontinuation, leucovorin calcium rescue, continuous renal replacement therapy, broad-spectrum anti-infection treatment, blood product transfusion, and invasive mechanical ventilation for progressive circulatory and respiratory failure.
Outcomes: Serial serum MTX remained elevated 6 days after the final dose. Despite full intensive supportive care, the patient died of refractory septic shock and irreversible multiorgan failure.
Lessons: Conventional-dose MTX is contraindicated for ESRD patients. Mandatory pre-prescription renal function assessment, regular laboratory monitoring, and folate supplementation are essential to prevent life-threatening MTX toxicity in high-risk elderly populations.
(Copyright © 2026 the Author(s). Published by Wolters Kluwer Health, LLC.)
Competing Interests: The authors have no funding and conflicts of interest to declare.
References: Krasselt M. Methotrexate - Safe backbone for the treatment of rheumatoid arthritis. Curr Rheumatol Rev. 2025;21:169–81.
Ouellette S, Shah R, Razi S, Ashforth G, Wassef C. Fatal low-dose methotrexate toxicity: a case report and literature review. Dermatol Ther. 2022;35:e15945.
Kystaubayeva Z, Zhakupbekova M, Mukhamedjanova A, Nurpeissova R. Hematological side effects of methotrexate in rheumatoid arthritis: a systematic review [published online ahead of print May 15, 2026]. Curr Rheumatol Rev. doi: 10.2174/0115733971454973260424092936. (PMID: 10.2174/0115733971454973260424092936)
Kanderi T, Gomez JC, Puthenpura MM, et al. Pancytopenia as a complication of low-dose methotrexate in a septuagenarian: a rare presentation. Cureus. 2020;12:e8492.
Javed K, Wijeratne R, Bandaru SK. The unseen danger of methotrexate toxicity. J Community Hosp Intern Med Perspect. 2023;13:39–42.
Ratanapokasatit Y, Jurairattanaporn N. Methotrexate-induced leukocytoclastic vasculitis: a case report and literature review. Clin Cosmet Investig Dermatol. 2025;18:2005–12.
Ebisawa K, Iwashita T, Uchiyama K, Kitayama Y, Takeuchi T. Epstein-Barr virus-positive mucocutaneous ulcer resulting in severe methotrexate intoxication: a case report. J Med Case Rep. 2024;18:409.
Smolen JS, Edwards CJ, Konzett V, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update. Ann Rheum Dis. 2026;85:991–1009.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4 Suppl):S117–314.
Surapaneni D, Dasi SC, Sam N, M J. Methotrexate toxicity-induced pancytopenia and mucocutaneous ulcerations in psoriasis. Cureus. 2024;16:e66222.
Corbisier T, Von Bueren AO, Breunis WB, et al. Role of molecular adsorbent recirculating system in methotrexate-induced acute liver failure: a case report and literature review. Front Pediatr. 2024;12:1424919.
Zhang L, Li J, Wang X, et al. Low-dose methotrexate adverse reaction risk in renal impairment: pharmacovigilance and physiological pharmacokinetic model assessment. Front Pharmacol. 2025;16:1703557.
Lui SW, Lu JW, Ho YJ, Hsieh T-Y, Yeh F-C, Liu F-C. IVIG as a promising therapy for methotrexate-induced life-threatening neutropenic enterocolitis in an elderly patient with rheumatoid arthritis: a case report and literature review. In Vivo. 2024;38:511–7.
Fahmy MM, Habib HA, Zeidan EM, Jardan YAB, Heeba GH. Alogliptin mitigates methotrexate-induced nephrotoxicity in a rat model: antagonizing oxidative stress, inflammation and apoptosis. Int J Mol Sci. 2025;26:9608.
Refeno V, Rasamimanana NG, Abasse BA, Ramarokoto MPM, Fanomezantsoa MJE, Randaoharison PG. Methotrexate-induced toxidermia and pancytopenia in a patient with ectopic pregnancy: a case report. J Med Case Rep. 2021;15:579.
Tome ACN, Santos KF, Lima EQ, Ramalho RJ. High-flux hemodialysis as rescue therapy for high-dose methotrexate toxicity: case series and clinical insights. Front Med (Lausanne). 2025;12:1495705.
Bielack SS, Soussain C, Fox CP, et al. A European consensus recommendation on the management of delayed methotrexate elimination: supportive measures, leucovorin rescue and glucarpidase treatment. J Cancer Res Clin Oncol. 2024;150:441.
Purzycki T, Knapp M, Patel S. Extracorporeal management of severe methotrexate toxicity and acute kidney injury in the absence of glucarpidase. BMJ Case Rep. 2025;18:e267929.
Contributed Indexing: Keywords: case report; end-stage renal disease; intoxication; methotrexate
Substance Nomenclature: YL5FZ2Y5U1 (Methotrexate)
0 (Antirheumatic Agents)
Entry Date(s): Date Created: 20260822 Date Completed: 20260822 Latest Revision: 20260918
Update Code: 20260918
PubMed Central ID: PMC13502829
DOI: 10.1097/MD.0000000000050331
PMID: 42629702
Βάση Δεδομένων: MEDLINE
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  Data: Fatal intoxication caused by conventional-dose methotrexate in an elderly patient with end-stage renal disease: A cautionary case report.
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  Data: <searchLink fieldCode="AU" term="%22He+Q%22">He Q</searchLink>; Department of Emergency, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.<br /><searchLink fieldCode="AU" term="%22Huang+X%22">Huang X</searchLink>; Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Rationale: Methotrexate (MTX) is a first-line agent for rheumatoid arthritis, and impaired renal excretion drastically elevates the risk of fatal drug accumulation. End-stage renal disease (ESRD) patients face an extreme toxicity risk even under conventional low-dose MTX, yet related fatal cases remain underreported. This case highlights critical clinical warnings for rheumatologists and emergency physicians.<br />Patient Concerns: A 71-year-old male with a 5-year history of rheumatoid arthritis and 1-year untreated chronic kidney disease stage 5 received weekly 10 mg subcutaneous MTX for 3 consecutive weeks without folic acid supplementation or regular laboratory monitoring. One day after his latest injection, he developed persistent nausea, vomiting, extensive oral ulcers, a skin rash, and drowsiness.<br />Diagnoses: Severe MTX intoxication complicated by profound bone marrow suppression, septic shock, and multiple organ dysfunction syndrome. Persistently elevated serum MTX confirmed impaired renal drug clearance in ESRD.<br />Interventions: Immediate MTX discontinuation, leucovorin calcium rescue, continuous renal replacement therapy, broad-spectrum anti-infection treatment, blood product transfusion, and invasive mechanical ventilation for progressive circulatory and respiratory failure.<br />Outcomes: Serial serum MTX remained elevated 6 days after the final dose. Despite full intensive supportive care, the patient died of refractory septic shock and irreversible multiorgan failure.<br />Lessons: Conventional-dose MTX is contraindicated for ESRD patients. Mandatory pre-prescription renal function assessment, regular laboratory monitoring, and folate supplementation are essential to prevent life-threatening MTX toxicity in high-risk elderly populations.<br /> (Copyright © 2026 the Author(s). Published by Wolters Kluwer Health, LLC.)
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  Label: Competing Interests
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  Data: The authors have no funding and conflicts of interest to declare.
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  Label: References
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  Data: Krasselt M. Methotrexate - Safe backbone for the treatment of rheumatoid arthritis. Curr Rheumatol Rev. 2025;21:169–81.<br />Ouellette S, Shah R, Razi S, Ashforth G, Wassef C. Fatal low-dose methotrexate toxicity: a case report and literature review. Dermatol Ther. 2022;35:e15945.<br />Kystaubayeva Z, Zhakupbekova M, Mukhamedjanova A, Nurpeissova R. Hematological side effects of methotrexate in rheumatoid arthritis: a systematic review [published online ahead of print May 15, 2026]. Curr Rheumatol Rev. doi: 10.2174/0115733971454973260424092936. (PMID: <searchLink fieldCode="PM" term="%2210%2E2174%2F0115733971454973260424092936%22">10.2174/0115733971454973260424092936)</searchLink><br />Kanderi T, Gomez JC, Puthenpura MM, et al. Pancytopenia as a complication of low-dose methotrexate in a septuagenarian: a rare presentation. Cureus. 2020;12:e8492.<br />Javed K, Wijeratne R, Bandaru SK. The unseen danger of methotrexate toxicity. J Community Hosp Intern Med Perspect. 2023;13:39–42.<br />Ratanapokasatit Y, Jurairattanaporn N. Methotrexate-induced leukocytoclastic vasculitis: a case report and literature review. Clin Cosmet Investig Dermatol. 2025;18:2005–12.<br />Ebisawa K, Iwashita T, Uchiyama K, Kitayama Y, Takeuchi T. Epstein-Barr virus-positive mucocutaneous ulcer resulting in severe methotrexate intoxication: a case report. J Med Case Rep. 2024;18:409.<br />Smolen JS, Edwards CJ, Konzett V, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update. Ann Rheum Dis. 2026;85:991–1009.<br />Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4 Suppl):S117–314.<br />Surapaneni D, Dasi SC, Sam N, M J. Methotrexate toxicity-induced pancytopenia and mucocutaneous ulcerations in psoriasis. Cureus. 2024;16:e66222.<br />Corbisier T, Von Bueren AO, Breunis WB, et al. Role of molecular adsorbent recirculating system in methotrexate-induced acute liver failure: a case report and literature review. Front Pediatr. 2024;12:1424919.<br />Zhang L, Li J, Wang X, et al. Low-dose methotrexate adverse reaction risk in renal impairment: pharmacovigilance and physiological pharmacokinetic model assessment. Front Pharmacol. 2025;16:1703557.<br />Lui SW, Lu JW, Ho YJ, Hsieh T-Y, Yeh F-C, Liu F-C. IVIG as a promising therapy for methotrexate-induced life-threatening neutropenic enterocolitis in an elderly patient with rheumatoid arthritis: a case report and literature review. In Vivo. 2024;38:511–7.<br />Fahmy MM, Habib HA, Zeidan EM, Jardan YAB, Heeba GH. Alogliptin mitigates methotrexate-induced nephrotoxicity in a rat model: antagonizing oxidative stress, inflammation and apoptosis. Int J Mol Sci. 2025;26:9608.<br />Refeno V, Rasamimanana NG, Abasse BA, Ramarokoto MPM, Fanomezantsoa MJE, Randaoharison PG. Methotrexate-induced toxidermia and pancytopenia in a patient with ectopic pregnancy: a case report. J Med Case Rep. 2021;15:579.<br />Tome ACN, Santos KF, Lima EQ, Ramalho RJ. High-flux hemodialysis as rescue therapy for high-dose methotrexate toxicity: case series and clinical insights. Front Med (Lausanne). 2025;12:1495705.<br />Bielack SS, Soussain C, Fox CP, et al. A European consensus recommendation on the management of delayed methotrexate elimination: supportive measures, leucovorin rescue and glucarpidase treatment. J Cancer Res Clin Oncol. 2024;150:441.<br />Purzycki T, Knapp M, Patel S. Extracorporeal management of severe methotrexate toxicity and acute kidney injury in the absence of glucarpidase. BMJ Case Rep. 2025;18:e267929.
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