Pancytopenia related eosinophilia in rheumatoid arthritis: a specific methotrexate phenomenon?

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.