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Pancytopenia related eosinophilia in rheumatoid arthritis: a specific methotrexate phenomenon?
G A Bruyn1, E Velthuysen, P Joosten
1Department of Rheumatology, Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands.
Abstract:
Methotrexate (MTX) induced pancytopenia has been reported in about 3% of patients with rheumatoid arthritis (RA) receiving low dose MTX. We describe 4 additional patients with RA (2M, 2F; mean age 65 yrs; mean duration of RA 9 yrs) who developed pancytopenia while receiving low dose MTX. Risk factors identified for the development of pancytopenia in our patients included impaired renal function, hypoalbuminemia, advanced age, low folate level, concurrent use of multiple comedication, nonsteroidal antiinflammatory drugs, and cotrimoxazole). Remarkably, pancytopenia related eosinophilia was observed in blood and bone marrow after restoring the intracellular folate level by folinic acid. The range of eosinophils was 22-56% of the number of peripheral white blood cells (mean nadir 33%). The peak level of eosinophilic granulocytes was reached after a mean of 6 days in hospital (range 4-8), whereas the peak of neutrophils was reached after a mean of 11 days (range 9-13 days). The duration of the eosinophilic response was 11 days. As eosinophilia has not been observed in other drug induced pancytopenias in patients with RA this could be a specific MTX induced phenomenon.
Insights
Methotrexate (MTX) can cause pancytopenia in rheumatoid arthritis patients. A specific eosinophilia was observed during treatment with folinic acid, suggesting a unique MTX-related effect.
Area of Science:
- Rheumatology
- Hematology
- Pharmacology
Background:
- Methotrexate (MTX) is a common treatment for rheumatoid arthritis (RA).
- MTX-induced pancytopenia occurs in approximately 3% of RA patients on low-dose therapy.
- Risk factors for MTX toxicity include renal impairment, hypoalbuminemia, and advanced age.
Observation:
- Four additional RA patients developed pancytopenia while on low-dose MTX.
- Risk factors identified included impaired renal function, hypoalbuminemia, advanced age, low folate, and concurrent medications (NSAIDs, cotrimoxazole).
- Pancytopenia-related eosinophilia was noted in blood and bone marrow after folinic acid treatment.
Findings:
- Eosinophil levels ranged from 22-56% of white blood cells.
- Peak eosinophilia occurred a mean of 6 days after hospitalization.
- This eosinophilia may be a specific phenomenon related to MTX-induced pancytopenia.
Implications:
- Recognizing MTX-induced pancytopenia and its specific eosinophilic response is crucial for RA patient management.
- Folinic acid administration can restore intracellular folate levels and potentially reverse MTX toxicity.
- Further research is needed to elucidate the mechanism of MTX-induced eosinophilia in RA patients.