Methotrexate-Induced Folate Deficiency Anemia
The most likely diagnosis is methotrexate-induced folate deficiency anemia, given the macrocytic anemia (MCV 108) developing over 3 months in a patient restarted on methotrexate without documented folate supplementation. 1
Clinical Reasoning
Why This Is Folate Deficiency from Methotrexate
Macrocytic anemia with elevated MCV is the hallmark finding of folate deficiency from methotrexate, which precisely matches this patient's presentation with hemoglobin of 7 and MCV of 108 1
The timeline is critical: Four months of methotrexate use without folate supplementation is a well-established risk factor for developing folate deficiency 1
Early bone marrow toxicity from methotrexate manifests as increased mean corpuscular volume, which can occur before frank anemia develops 1
The FDA drug label confirms that methotrexate can suppress hematopoiesis and cause anemia, with pancytopenia occurring even after prolonged use 2
Why Other Diagnoses Are Less Likely
Anemia of chronic disease from rheumatoid arthritis is excluded because it typically presents as normocytic or microcytic anemia, not macrocytic 1
While rheumatoid arthritis itself can cause anemia, the elevated MCV of 108 and the temporal relationship to methotrexate reinitiation make drug-induced folate deficiency the primary diagnosis 1
Vitamin B12 deficiency could cause macrocytic anemia, but the recent methotrexate exposure without folate supplementation makes folate deficiency more likely in this specific clinical context 3
Immediate Management
Discontinue Methotrexate
Methotrexate must be discontinued immediately until hematologic parameters normalize 1
The FDA label specifies that in rheumatoid arthritis, methotrexate should be stopped immediately if there is a significant drop in blood counts 2
Folate Repletion
When restarting methotrexate, mandatory folate supplementation with 1-5 mg daily is required 1
Folic acid supplementation at least 5 mg per week reduces gastrointestinal and liver toxicity without compromising methotrexate efficacy 4
Monitoring Protocol
CBC should be monitored every 3-4 months after the first 1-2 months of methotrexate therapy 1
The FDA label recommends monitoring CBC, creatinine, and liver function tests every 1-1.5 months until a stable dose is reached, then every 1-3 months thereafter 2
Withhold or decrease methotrexate dose if MCV exceeds 105 fL 1
Critical Pitfalls to Avoid
Never restart methotrexate without concurrent folate supplementation - this is the most common preventable cause of methotrexate-induced anemia 1
Do not assume that anemia in a rheumatoid arthritis patient is solely due to chronic disease; always check MCV and consider drug-induced causes 1
Pancytopenia can occur after even a single dose of methotrexate in patients with risk factors, so baseline and regular monitoring is essential 1
The case report literature documents that multiple factors can contribute to methotrexate toxicity, including concurrent sulfasalazine use and vitamin B12 deficiency, so comprehensive evaluation is warranted 3