Presentation Type
Poster
Discipline Track
Patient Care
Abstract Type
Case Report
Abstract
Introduction: Methotrexate(MTX) is a widely used disease-modifying antirheumatic drug for various conditions including autoimmune diseases or malignancies. Pancytopenia as an adverse effect of methotrexate is rarely reported but sometimes fatal, and requires more attention. This case report shows a 76-year-old woman with a history of rheumatoid arthritis(RA) on MTX therapy, presenting with severe pancytopenia and oral lesions, and highlights the importance of safe medication practices especially in elderly patients with poor health literacy and compliance.
Case Presentation: A 76-year-old female with rheumatoid arthritis presented to the emergency department with a worsening oral lesion. She had been on an unspecified maintenance dose of MTX for the management of RA for more than 2 years without adequate follow-ups. On initial evaluation, the patient had multiple ulcerative lesions in her oral cavity involving buccal mucosa and soft palate, and severe gingivitis in the upper and lower gumline, associated odynophagia. She also had similar ulcerative lesions in the genitalia with vaginal bleeding. On initial labs, she had severe pancytopenia with hemoglobin(Hb) 8.6 g/dL, white blood cell(WBC) count 670/uL with absolute neutrophil count(ANC) 300/uL, and platelet(PLT) 12,000/uL. It was a dramatic change compared to the lab 3 months ago showing Hb 10.7g/dL, WBC 4,710/uL, and PLT 142,000/uL.
As an initial investigation of pancytopenia and newly developed mouth ulcers, broad differentials are discussed including primary bone marrow(BM) disorder, medication-induced pancytopenia, nutritional deficiencies, infectious disease, and autoimmune disease. Autoimmune panels including ANA and ANCA came out negative. Vitamin B12 and Folic acid levels were above normal limits, and infectious workup with HIV antibody and RPR tests came out negative. Peripheral blood smear revealed pancytopenia but didn’t reveal myeloid or blast cells. BM biopsy revealed markedly hypocellular BM with 2~3% cellularity. Flow cytometry did not reveal any abnormalities. The methotrexate level that was drawn on day 2 of admission was unremarkable.
With the ambiguous diagnosis of methotrexate-induced pancytopenia versus aplastic anemia, the patient was started on eltrombopag, which was discontinued on day 5 with dramatic improvement in all cell lineages. Upon discharge, the patient was put off the methotrexate and was closely monitored in the outpatient setting without treatment for pancytopenia. The patient continued to maintain the recovered state of all cell lineages, which is more suggestive of drug-induced pancytopenia
Discussion: MTX-induced pancytopenia is a rare but severe complication observed in patients undergoing high-dose infusion therapy or long-term maintenance therapy with a possible pathophysiology being interference of DNA synthesis by inhibition of dihydrofolate reductase, leading to BM suppression. Although MTX is a widely used medication, safety education for physicians and patients has fallen short. For patients with rheumatologic diseases, the initial and the maintenance dose and duration of this medication differ greatly and toxicities should be closely monitored with proper education. Especially in elderly patients with a poor understanding of the disease, adverse effects can be seen more frequently and safety education is warranted.
Academic/Professional Position
Resident
Mentor/PI Department
Internal Medicine
Recommended Citation
Cho, Eunbee; Daza, Jessica Marcela; Park, Jiye A.; Patel, Shreel; Choi, Seokwon; and Farray, Daniel, "Methotrexate-Induced Pancytopenia: A Call For Mindful Medication Practices" (2024). Research Symposium. 48.
https://scholarworks.utrgv.edu/somrs/2024/posters/48
recovery of three cell lineages
methotrexate levels with time.jpg (53 kB)
serum methotrexate levels with time, reference
Included in
Methotrexate-Induced Pancytopenia: A Call For Mindful Medication Practices
Introduction: Methotrexate(MTX) is a widely used disease-modifying antirheumatic drug for various conditions including autoimmune diseases or malignancies. Pancytopenia as an adverse effect of methotrexate is rarely reported but sometimes fatal, and requires more attention. This case report shows a 76-year-old woman with a history of rheumatoid arthritis(RA) on MTX therapy, presenting with severe pancytopenia and oral lesions, and highlights the importance of safe medication practices especially in elderly patients with poor health literacy and compliance.
Case Presentation: A 76-year-old female with rheumatoid arthritis presented to the emergency department with a worsening oral lesion. She had been on an unspecified maintenance dose of MTX for the management of RA for more than 2 years without adequate follow-ups. On initial evaluation, the patient had multiple ulcerative lesions in her oral cavity involving buccal mucosa and soft palate, and severe gingivitis in the upper and lower gumline, associated odynophagia. She also had similar ulcerative lesions in the genitalia with vaginal bleeding. On initial labs, she had severe pancytopenia with hemoglobin(Hb) 8.6 g/dL, white blood cell(WBC) count 670/uL with absolute neutrophil count(ANC) 300/uL, and platelet(PLT) 12,000/uL. It was a dramatic change compared to the lab 3 months ago showing Hb 10.7g/dL, WBC 4,710/uL, and PLT 142,000/uL.
As an initial investigation of pancytopenia and newly developed mouth ulcers, broad differentials are discussed including primary bone marrow(BM) disorder, medication-induced pancytopenia, nutritional deficiencies, infectious disease, and autoimmune disease. Autoimmune panels including ANA and ANCA came out negative. Vitamin B12 and Folic acid levels were above normal limits, and infectious workup with HIV antibody and RPR tests came out negative. Peripheral blood smear revealed pancytopenia but didn’t reveal myeloid or blast cells. BM biopsy revealed markedly hypocellular BM with 2~3% cellularity. Flow cytometry did not reveal any abnormalities. The methotrexate level that was drawn on day 2 of admission was unremarkable.
With the ambiguous diagnosis of methotrexate-induced pancytopenia versus aplastic anemia, the patient was started on eltrombopag, which was discontinued on day 5 with dramatic improvement in all cell lineages. Upon discharge, the patient was put off the methotrexate and was closely monitored in the outpatient setting without treatment for pancytopenia. The patient continued to maintain the recovered state of all cell lineages, which is more suggestive of drug-induced pancytopenia
Discussion: MTX-induced pancytopenia is a rare but severe complication observed in patients undergoing high-dose infusion therapy or long-term maintenance therapy with a possible pathophysiology being interference of DNA synthesis by inhibition of dihydrofolate reductase, leading to BM suppression. Although MTX is a widely used medication, safety education for physicians and patients has fallen short. For patients with rheumatologic diseases, the initial and the maintenance dose and duration of this medication differ greatly and toxicities should be closely monitored with proper education. Especially in elderly patients with a poor understanding of the disease, adverse effects can be seen more frequently and safety education is warranted.