Treatment of Felty's syndrome with the haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF)

Abstract

Felty's syndrome (FS) (rheumatoid arthritis with neutropenia and splenomegaly) has a poor prognosis, largely because of the high risk of severe infection. Granulocyte colony-stimulating factor (G-CSF) is an emerging treatment for chronic neutropenia. We prospectively monitored its use in eight patients with recurrent infections or who required joint surgery. Significant side-effects were documented in five, including nausea, malaise, generalized joint pains, and in one patient, a vasculitic skin rash. In two patients treatment had to be stopped, and in these cases G-CSF had been started at full vial dosage (300 micrograms/ml filgrastim or 263 micrograms/ml lenograstim) alternate days or daily. G-CSF treatment was continued in three patients by restarting at reduced dose, and changing the proprietary formulation. G-CSF raised the neutrophil count, reduced severe infection, and allowed surgery to be performed. A combined clinical and laboratory index suggested that long-term treatment (up to 3.5 years) did not exacerbate the arthritis. Once on established treatment, it may be possible to use smaller weekly doses of G-CSF to maintain the same clinical benefit. One of the three patients whose FS was associated with a large granular T-cell lymphocytosis showed a reduction in this subset of lymphocytes during G-CSF treatment.

Granulocyte colony-stimulating factor treatment for cyclophosphamide-induced severe neutropenia in Wegener's granulomatosis

“…The most common side effect is transient nonarticular bone pain in up to 20% of patients, while local reactions at the injection site or an increase in serum alkaline phosphatase or uric acid levels are definitely less common (6). Treatment with rHuG-CSF has also been proven to be effective in the long-term management of patients with severe chronic neutropenia, a chronic deficiency of neutrophils of unknown origin associated with recurrent bacterial infections, and in patients with Felty's syndrome (6,12,16). However, in those patients, the spectrum of side effects was somewhat different from that in patients with neutropenia due to antineoplastic treatment, in that induction of cutaneous vasculitis was observed in a number of the former patients but only very rarely in the latter (6,8,9,16).…”

“…The literature to date describes a total of 26 cases of cutaneous vasculitis and a few cases of neutrophilic dermatoses (such as Sweet's syndrome) in association with rHuG-CSF (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). The diagnosis of leukocytoclastic vasculitis was confirmed by skin biopsy in 15 cases (8,10,11,15).…”

“…Clinical experience suggests that growth factor treatment is also efficacious against severe neutropenia secondary to immunosuppressive treatment (6,7). On the other hand, several patients receiving long-term treatment with rHuG-CSF for severe chronic neutropenia or Felty's syndrome have developed cutaneous vasculitis that was apparently treatment induced (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Based on these reports, caution has been advocated in the use of hematopoietic growth factors in patients with vasculitis and other autoimmune disorders (13), but no solid data on the risks and benefits of this treatment, particularly in vasculitis patients, appear to be available.…”

Esplenomegalia gigante por síndrome de Felty

“…Por tratarse de un síndrome raro, se torna difícil realizar estudios clínicos controlados y randomizados sobre su manejo clínico. Entre las opciones terapéuticas se destacan el metotrexate, el factor estimulador de colonias de granulocitos, además de la [12][13][14] esplenectomía.…”

“…Representa un alto costo y su administración es 13 subcutánea. 10,13 El metotrexate es considerado la droga de elección para el tratamiento del síndrome de Felty.…”