Felty's syndrome: favorable response to granulocyte-macrophage colony-stimulating factor in the acute phase.

We report a case of Felty's syndrome in which infectious complications due to severe neutropenia could be overcome by short-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 7 micrograms/kg/day s.c.). Leukocyte counts rose from 1,050/mm3 at presentation to 4,470/mm3 after 15 days of treatment. A flare-up of arthritis was not noted. Defects in granulocyte function and clinical improvement prior to leukocyte rise suggest that the beneficial effect of GM-CSF is mainly due to an improvement of granulocyte function.     

Treatment of neutropenia in Felty's syndrome with granulocyte-macrophage colony-stimulating factor — hematological response accompanied by pulmonary complications with lethal outcome

Summary We report on a 67-year-old man with Felty's syndrome (FS) complicated by recurrent pneumonia and an infected wound, which was not healing in spite of maximal antibiotic and local therapy. Encouraged by previous experience, we treated him with granulocyte-macrophage colony-stimulating factor (GM-CSF). His total leukocyte count rose, but the patient's pneumonia deteriorated. In addition, a previously known chronic obstructive lung disease (COLD) was exacerbated acutely. These complications finally led to his death. Postmortem examination revealed widespread pneumonia with invasive aspergillosis and a peripheral adenocarcinoma in his left lung.     

Flare of arthritis with successful treatment of Felty's syndrome with granulocyte colony stimulating factor (GCSF)

Summary A 58-year-old white male with Felty's syndrome was successfully treated with granulocyte colony stimulating factor (GCSF). GCSF can correct the granulocytopenia of Felty's syndrome and may be a beneficial therapeutic adjunct in patients who have serious infections associated with neutropenia. The patient developed a flare of arthritis concomitant with increased circulating neutrophils following GCSF therapy.     

Cytotoxic chemotherapy for cancer in Felty''s syndrome: role of lithium carbonate

A 61-yr-old white man with Felty's syndrome, who had previously undergone splenectomy, presented for cytotoxic chemotherapy. Random granulocyte counts remained low, prohibiting the initiation of such treatment. A trial of lithium carbonate was instituted, resulting in prompt elevation of granulocyte counts into the normal range. Cytotoxic chemotherapy was then administered, and fluctuations of neutrophil counts similar to those of hematologically normal individuals were observed.     

Treatment of severe neutropenia due to Felty's syndrome or systemic lupus erythematosus with granulocyte colony-stimulating factor.

OBJECTIVES: To examine the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for the treatment of severe neutropenia due to Felty's syndrome (FS) or systemic lupus erythematosus (SLE). METHODS: Eight patients with absolute neutrophil counts (ANC) below 1,000/microL attributable to FS (n = 4) or SLE (n = 4) were treated with rhG-CSF. The hematologic and clinical response as well as side effects were recorded. In addition, reports on the use of rhG-CSF/rhGM-CSF in FS and SLE retrieved from the English language literature were analyzed. RESULTS: RhG-CSF effectively corrected neutropenia due to FS and SLE in seven of the current eight patients. In 54 of 55 FS and SLE patients retrieved from the literature, G-CSF or GM-CSF, respectively, proved to be effective at elevating the neutrophil count, which was often associated with improvement of infectious complications. The neutrophil count often declined again when growth factor treatment was stopped but generally stabilized at a level that exceeded the pretreatment count. Side effects included rare cases of thrombocytopenia, arthralgias, and development of cutaneous leukocytoclastic vasculitis. Side effects were dose dependent and resolved when treatment was discontinued. One of our own patients and 17 previously reported patients continued to benefit from long-term administration of rhG-CSF over periods of more than 40 months. CONCLUSIONS: RhG-CSF is an effective and generally well-tolerated treatment for neutropenia due to FS or SLE. Exacerbation of the underlying rheumatic condition due to G-CSF appears to be rare if G-CSF is administered at the lowest dose effective at elevating the ANC above 1,000/microL.     

Chronic neutropenia associated with autoimmune disease

Chronic neutropenia with autoimmune diseases is associated mainly with rheumatoid arthritis (RA), as Felty's syndrome or large granular lymphocyte (LGL) leukemia, and with systemic lupus erythematosus (SLE). Recent advances have allowed better understanding regarding the mechanism of neutropenia and improved options for treatment. Target antigens for antineutrophil antibodies have been identified for both Felty's syndrome and for SLE. The role of soluble Fas-ligand (FasL) in inducing apoptosis of neutrophils has been clarified for LGL leukemia and increased neutrophil apoptosis has been described in neutropenic patients with SLE. The role of immune complexes in affecting neutrophil traffic and function continues to be studied. Treatments of neutropenia have included methotrexate, cyclosporine A, and granulocyte colony-stimulating factor (G-CSF) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF). The efficacy of both GM- and G-CSF in reversing neutropenia and decreasing the risk of infections in Felty's syndrome and SLE has been well documented. Of concern, however, have been flares of symptoms or development of leukocytoclastic vasculitis in some patients following the use of these cytokines. Recent results suggest that in these patients G-CSF should be administered at the lowest dose effective at elevating the neutrophil count above 1,000/microL.     

Reversal of depressed neutrophil superoxide production in Felty's syndrome after gold therapy

Six patients with Felty's syndrome were reevaluated after a course of chrysotherapy. In 5 patients, white cells and absolute neutrophil counts had returned to normal. In 4 of these, there was significant concomitant improvement in neutrophil function as assessed by the ability of cells to generate superoxide radicals.     

Cyclosporine for the treatment of granulocytopenia in Felty's syndrome

A patient with Felty's syndrome was treated with cyclosporine, initially 10 mg/kg/day and then 4 mg/kg/day. The neutrophil count increased by 6 weeks and was normal at 3 months. Over the subsequent 27 months the neutrophil count was closely related to the cyclosporine dosage and there was no evidence of cyclosporine toxicity. This case indicates that cyclosporine may have a role in the treatment of Felty's syndrome.     

Prevalence of granular lymphocyte proliferation in patients with rheumatoid arthritis and neutropenia

PURPOSE: Granular lymphocyte proliferation and neutropenia with or without splenomegaly occurs with unknown frequency in rheumatoid arthritis. We decided to evaluate the prevalence of Felty's syndrome and granular lymphocyte proliferation among patients with rheumatoid arthritis and to determine the fraction of patients with granular lymphocyte proliferation who also had rheumatoid arthritis. PATIENTS, METHODS, AND RESULTS: We retrospectively analyzed 1,053 cases of rheumatoid arthritis and 13,505 marrow examination reports for the decade 1978 to 1987. Among patients with Felty's syndrome rheumatoid arthritis with neutropenia/leukopenia, and rheumatoid arthritis with splenomegaly, we identified 18 patients with neutropenia as a manifestation of rheumatoid arthritis. We also identified marrow examinations in 150 patients with rheumatoid arthritis. Using blood counts, microscopy of marrow, and surface antigen analysis of mononuclear cells, we determined that 12 patients had typical Felty's syndrome and six had granular lymphocyte proliferation, representing prevalences of 1.1 percent and 0.6 percent, respectively. No patient had granular lymphocyte proliferation without neutropenia. CONCLUSION: Granular lymphocyte proliferation and neutropenia with or without splenomegaly in rheumatoid arthritis commonly resembles typical Felty's syndrome. Further, the six patients with granular lymphocyte proliferation represent 20 percent of our institution's patients with granular lymphocyte proliferation, supporting the previously described common association of this disorder with rheumatoid arthritis. The relatively large fraction of deaths (due to malignancy and infection) among the patients with typical Felty's syndrome suggests that their mean survival may be comparatively less than in those with granular lymphocyte proliferation.     

Felty's syndrome: long-term followup after treatment with auranofin

Five patients who had Felty's syndrome were treated with auranofin, 6 mg/day, for a period that ranged from 4 months to 2 years. All patients experienced both an improvement in articular symptoms and a normalization of the leukocyte count. Auranofin appears to be an effective treatment for Felty's syndrome, and to have a lower degree of toxicity than parenteral gold.     

Primary aspergillosis of the larynx in a patient with Felty's syndrome

Herein we report the first case of primary aspergillosis of the larynx in a patient with Felty's syndrome. A 53-year-old man, a florist by profession, with a 12-year history of rheumatoid arthritis and on treatment with steroids, was admitted because of hoarseness, and intermittent fever of 2 weeks' duration. On admission, physical examination and laboratory data showed, among other findings, splenomegalia and neutropenia. At bone marrow examination, normal cellularity with mild dyserythropoiesis was observed. A fiberoptic laryngoscopy showed white plaques on both the true vocal cords. Both culture and microscopic examination of these lesions provided the diagnosis of invasive process by Aspergillus flavus. A computed tomography of the middle ears, paranasal sinuses, and chest was normal. Thus, primary aspergillosis of the larynx and Felty's syndrome was diagnosed, and the patient was successfully treated with granulocyte colony-stimulating factor and systemic antifungal agents. Felty's syndrome, corticosteroid use, and occupational risk probably rendered our patient susceptible to Aspergillus infection.     

ARTICULAR DISEASE SEVERITY IN RHEUMATOID SUBJECTS WITH AND WITHOUT FELTY'S SYNDROME

Articular disease severity as measured by a radiographic scoreof hands and feet was compared in rheumatoid subjects with (21)and without (170) Felty's syndrome. Disease duration was a majordeterminant of joint destruction. When this was taken into considerationradiographic scores were no higher in the Felty's group thanin rheumatoid subjects without Felty's syndrome. Immunogeneticassociations previously described in Felty's syndrome are unlikelytherefore to represent non—specific markers of diseaseseverity and more likely to represent markers of extra—articulardisease. KEY WORDS: Radiological scoring, Felty—s syndrome     

Long-term correction of neutropenia in Felty's syndrome with granulocyte colony-stimulating factor

Summary Neutropenia in Felty's Syndrome predisposes patients to recurrent bacterial infections. We have treated a patient for more than one year with G-CSF and ascertained that this growth factor can savely correct neutropenia over a long periode of time. G-CSF may constitute a new agent for the treatment and prophylaxis of infection in Felty's syndrome.     

ANTINUCLEAR AND ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA) IN THE SERA OF PATIENTS WITH FELTY'S SYNDROME

The prevalence of antinuclear (ANA) and antineutrophil cytoplasmicantibodies (ANCA) has been studied in the sera of 62 patientswith rheumatoid arthritis and 32 patients with Felty's syndrome.The presence of ANA was less in RA than Felty's syndrome (37%versus 69%). Specific autoantibody identification, where possible,was usually of SS-A or SS-B although two sera from patientswith Felty's syndrome had low levels of DNA antibody. ANCA wasdetected in the sera of 33% of patients with Felty's syndromeand was absent in RA sera. The pattern of ANCA staining waseither of a diffuse homogenous cytoplasmic or peripheral (pANCA)nature. Classical cytoplasmic granular staining (cANCA) wasnot identified. KEY WORDS: Antinuclear antibodies, Antineutrophil cytoplasmic antibodies (ANCA), Felty's syndrome     

Felty''s syndrome. Clinical and serological analysis of 34 cases.

Review of 34 cases of Felty's syndrome showed this to be a form of 'super' rheumatoid disease because of the severity of joint disease, the prominence of extra-articular features and the remarkable incidence of infection. The response to splenectomy in these 34 patients was shown by a return towards normal of peripheral blood abnormalities and a decrease in bone marrow granulopoiesis. Although some patients remained free of infection after splenectomy, others have continued to have infections despite the return of white blood cell counts to normal levels. Although splenectomy and subsequent increase in white blood cell levels may be beneficial, our experience suggests that other factors are important in the susceptibility to infection of Felty's syndrome patients. Moreover, we think that splenectomy may have been instrumental in the fatal infection of one of our patients.     

Low Fcgamma receptor III and high granulocyte colony-stimulating factor serum levels correlate with the risk of infection in neutropenia due to Felty's syndrome or systemic lupus erythematosus

PURPOSE: To determine whether serum levels of soluble Fcgamma receptor III and granulocyte colony-stimulating factor (G-CSF) are associated with the risk of infection in patients with neutropenia due to Felty's syndrome or systemic lupus erythematosus. SUBJECTS AND METHODS: Serum levels of G-CSF and soluble Fcgamma receptor III were measured by enzyme-linked immunosorbent assays in 13 patients with neutropenia due to Felty's syndrome, 10 patients with neutropenia due to systemic lupus erythematosus, and 41 controls with normal leukocyte counts (25 with systemic lupus erythematosus, 16 with rheumatoid arthritis). We calculated the area under the receiver operating characteristic (ROC) curves for the absolute neutrophil count, soluble Fcgamma receptor III levels, and G-CSF levels. RESULTS: Nine of the neutropenic patients (7 with Felty's syndrome, 2 with lupus) had one or more infections within 3 months before and after blood samples were obtained. Absolute neutrophil counts were similar in neutropenic patients who did or did not have infections. However, the median level of soluble Fcgamma receptor III (63 vs. 126 arbitrary units, P = 0.005) was significantly lower among patients who developed infections, whereas the median level of G-CSF (90.9 vs. 53.3 pg/mL, P = 0.04) was significantly higher compared with patients without infections. The area under the ROC curve was 0.58 (P = 0.49) for the absolute neutrophil count, 0.84 (P = 0.007) for soluble Fcgamma receptor III levels, and 0.73 (P = 0.03) for G-CSF levels. CONCLUSION: In patients with chronic neutropenia due to rheumatic diseases, low soluble Fcgamma receptor III levels and elevated G-CSF levels are better indicators of the risk of infection than is the neutrophil count.     

Methotrexate treatment in Felty's syndrome

Felty's syndrome is a rare disorder characterized as a systemic manifestation of severe rheumatoid arthritis associated with granulocytopenia and splenomegaly. We report a retrospective analysis of a series of seven patients treated successfully with low-dose methotrexate. leading to sustained clinical improvement (number of swollen joints) and normalization of the granulocyte count for an observation period of 1 yr. Our cohort is the largest ever published with methotrexate treatment of this rare condition. Our results confirm earlier single case reports suggesting methotrexate to be the first- choice treatment nowadays in Felty's syndrome.      

Spontaneous remission of Felty's syndrome.

The clinical course of a patient with Felty's syndrome is described. This patient was unusual because during a 3-year period of splenomegaly and leukopenia she did not develop repeated infections, leg ulcers, or other complications of Felty's syndrome. Then a spontaneous remission began. During the subsequent 6 years, neither symptoms nor signs of Felty's syndrome have recurred.     

Coexistent Felty''s syndrome and palindromic rheumatism.

Palindromic rheumatism is a syndrome of intermittent abrupt onset monoarthritis with asymptomatic intercritical periods of variable duration, which commonly evolves into rheumatoid arthritis. Felty's syndrome consists of leucopenia (selective neutropenia) and splenomegaly, usually occurring in longstanding classic rheumatoid arthritis. Felty's syndrome can be confused with the more recently recognised rheumatoid arthritis associated large granular lymphocyte proliferative disease. This paper describes a patient with palindromic rheumatism presenting with Felty's syndrome in whom large granular lymphocyte proliferative disease was ruled out by lymphocyte phenotyping.     

D-penicillamine in Felty's syndrome

We report our experience with 8 patients with Felty's syndrome who were treated with D-penicillamine for a mean of one year. Six of the 8 patients experienced improvement in their neutropenia. Cutaneous ulcers healed in 4 of 6, while recurrent infections cleared in 3 of 5 patients. The drug was withdrawn in 6 patients--lack of response in one, thrombocytopenia in one, urticaria in one, rash in one, and granulocytopenia in 2. One of the latter 2 patients developed pancytopenia and died. Although D-penicillamine is effective in treatment of Felty's syndrome, its side effects can be serious and potentially lethal. Its use should be limited to patients who have failed other treatments.