FELTYS-SYNDROME - RISKS AND BENEFITS OF TREATMENT WITH HEMATOPOIETIC GROWTH-FACTORS

Felty's syndrome is a complication of rheumatoid arthritis whereby pat ients develop neutropenia of varying severity. Although the main clini cal concern is the development of serious infections, often patients r emain asymptomatic or continue with clinical problems related to the r heumatoid arthritis and not to the neutropenia, There is now considera ble clinical experience with the use of the recombinant human haemopoi etic growth factors granulocyte and granulocyte-macrophage colony-stim ulating factors (G-CSF and GM-CSF) in the treatment of patients with F elty's syndrome. The only indication for the use of either growth fact or for Felty's syndrome is the onset of infectious complications, whic h may be recurrent and serious, In general, when this occurs, the neut ropenia is severe (< 10(8) cells/L), The mechanism(s) underlying devel opment of the neutropenia in Felty's syndrome is similar to that in ot her forms of immune-mediated neutropenia, and in general is associated with a terminal defect in neutrophil maturation, It is likely that th e maturational defect is a consequence of 'immune based' inhibition, a lthough we lack detailed understanding of this inhibitory process, Gro wth factor therapy does not relieve the defect in terminal maturation, but in general may induce a significant improvement in the peripheral white cell count, Instances where growth factor therapy does not work appear to be due to an inability to overcome the maturational defect, Thus, the level of granulopoietic inhibition mediated by the rheumato id process varies in severity among patients. To date, treatment optio ns for Felty's syndrome have included disease-modifying antirheumatic drugs, corticosteroids and splenectomy, The addition of growth factor therapy is a welcome addition to these less than optimal treatment opt ions. However, all of the above therapies fail on occasion. Moreover, the dosage and frequency of growth factors must be titrated to keep th e white blood cell count < 5 x 10(9) cells/L, since overshoot may resu lt in complications, the most common being exacerbation of the rheumat oid arthritis. Another mechanism by which these drugs may exacerbate r heumatoid arthritis is through activation of neutrophils. The addition of disease modifying drugs may relieve the maturational defect, impro ve the peripheral white cell count and minimise disease exacerbation b y limiting neutrophil exposure to the administered haemopoietic growth factor. However, long term monotherapy with G-CSF has been successful ly employed without requiring disease-modifying therapy.