Unusual T cell proliferations and neutropenia in rheumatoid arthritis: comparison with classical Felty's syndrome

4 patients are described with rheumatoid arthritis, splenomegaly, neutropenia and an unusual proliferation of T cells in the blood and marrow. These patients are clinically similar to patients with classical Felty's syndrome but can be distinguished from them by staining blood and marrow mononuclear cells with a panel of monoclonal anti-T cell antibodies. The T cells from patients with T cell proliferations stain with UCHT1 (OKT3 equivalent) and UCHT4 (OKT8 equivalent but do not stain with a panel of OKT1-like antibodies. In 7 patients with classical Felty's syndrome there was no increase of UCHT4 cells in the blood and the large majority of T cells stained with OKT1-like antibodies. The marrows from the patients with T cell proliferations contain plentiful haemopoietic progenitor cells and it is probable that the T lymphocytes suppress their normal maturation. There was a poor response to splenectomy in 2 patients with T cell proliferations, and single cytotoxic drug therapy may be more appropriate when therapy is required. The literature is reviewed and it is suggested that the T cell proliferations may be secondary to the rheumatoid process.     

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.     

Reversal of neutropenia with methotrexate treatment in patients with Felty's syndrome. Correlation of response with neutrophil-reactive IgG

We evaluated the clinical and hematologic response to methotrexate (MTX) in 4 women with Felty's syndrome (FS) who had had neutropenia for 1-3 years. Since immune complexes or antineutrophil antibodies are implicated in the pathogenesis of the neutropenia of FS, we also measured both direct and indirect levels of neutrophil-reactive IgG. All 4 patients showed a prompt and dramatic increase in neutrophil counts within 1-2 months of starting MTX therapy. In 3 patients, the symptoms of arthritis also improved; in the fourth patient, arthritis worsened. Recurring infections ceased in 3 patients. Neutrophil-reactive IgG levels, which were elevated in all patients prior to treatment, decreased toward normal while the patients were receiving MTX therapy. We conclude that MTX is effective in treating the neutropenia of FS, in part by lowering neutrophil-reactive IgG.     

G-CSF versus GM-CSF in the treatment of neutropenia in a patient with Felty's syndrome on hemodialysis

We describe a patient with Felty's syndrome and chronic renal failure due to secondary amyloidosis in a periodic haemodialysis programme, who was successfully treated for neutropenia with sequential administration of colony-stimulating factors: granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor.     

Improvement of pancytopenia and articular and by splenectomy in a patient with Felty's syndrome]

A forty seven year-old woman with a 18 years history of rheumatoid arthritis presented with recurrent infection and pancytopenia. A diagnosis of Felty's syndrome was made hand on clinical and laboratory findings. In spite of drug therapy using nonsteroidal anti-inflammatory drugs, D-penicillamine and corticosteroid, the hematological abnormalities and active joint symptoms continued. Recurrences of severe bacterial infection and the rupture of esophageal varices necessitated splenectomy. Soon after the operation, dramatic improvement of hematological abnormalities were observed. Furthermore, after 3 months postoperatively, marked decrease in rheumatoid activities and disappearance of subcutaneous nodules were noticed. Titer of rheumatoid factor also showed a significant reduction and became negative 6 months after the operation. Although the efficacy of splenectomy on hematological abnormalities in Felty's syndrome has been well documented, its effect on rheumatic disease has not been clarified. The case presented here might suggested that suppression of reticuloendothelial system may have therapeutic effects in rheumatoid arthritis. The possible mechanisms involved in these findings have been discussed.     

Improvement of pneumonia and arthritis in Felty's syndrome by treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF)

Summary A 63-year old man with Felty's syndrome and pneumonia of unknown origin was treated with GM-CSF. Granulocyte counts increased and arthritis-related symptoms improved under GM-CSF. Pneumonia was treated effectively with antibiotics only during or after GM-CSF application. This suggests, that antibiotic-resistent infections can be treated effectively in patients with Felty's syndrome when granulocyte counts are raised by GM-CSF.     

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.     

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.     

Felty's syndrome treated with rhG-CSF associated with flare of arthritis and skin rash

Summary A patient with Felty's syndrome and rheumatoid arthritis was treated with recombinant granulocyte stimulating factor rhG-CSF (Neupogen) in view of severe neutropenia. He had a prompt rise in his neutrophil count and associated with this a severe flare of his arthritis and a skin rash. rhG-CSF was stopped, his neutrophil count fell rapidly and his symptoms resolved. rhG-CSF and the resulting rise in neutrophil count may be associated with flare of autoimmune disease in susceptible individuals.     

Phagocytosis and intracellular killing by polymorphonuclear cells from patients with rheumatoid arthritis and Felty's syndrome

The present in vitro study concerned the phagocytosis and intracellular killing by polymorphonuclear cells (PMN) of 5 patients with rheumatoid arthritis (RA) and 12 patients with Felty's syndrome (FS). PMN phagocytosis was assessed by microbiologic and morphologic methods, and intracellular killing was measured independently of continuous phagocytosis of viable bacteria (Staphylococcus aureus). PMN from patients with RA or FS ingested S aureus opsonized with immunoglobulins and complement as effectively as did PMN from healthy donors. However, the capacity of patient PMN to ingest S aureus opsonized with sera lacking complement activity, e.g., heat-inactivated donor serum and the sera of 2 patients with FS, was lower than that of healthy donor PMN. This decreased ingestion is associated with diminished expression of Fc receptors on the membrane of PMN from patients who have RA or FS. As with sera lacking complement activity, decreased capacity to ingest S aureus was observed after preloading donor PMN with immune aggregates, which also decreased the expression of Fc receptors. PMN from patients with RA or FS were found to be as active in killing S aureus as cells from healthy donors.     

Superoxide production in neutrophils of patients with rheumatoid arthritis and Felty's syndrome

The production of superoxide by N-formylmethionyl-leucyl-phenylalanine activated neutrophils was measured prospectively with a ferricytochrome C reduction assay in 33 normals, 33 patients with rheumatoid arthritis and 9 patients with Felty's syndrome. Both the rate and quantity of superoxide production were significantly lower in patients with Felty's syndrome when compared to the other 2 groups. This finding suggests a possible additional factor in the increased propensity of these patients to develop infections.     

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.     

Successful treatment of splenic lymphoma with villous lymphocytes by rituximab and laparoscopic splenectomy

We report on a case of splenic lymphoma with villous lymphocytes (SLVL) which responded well to rituximab. A 50-year-old man was admitted because of splenomegaly. Abnormal lymphocytes of B cell lineage with moderately basophilic cytoplasm and unevenly distributed villi (villous cells) were found, both in the peripheral blood and bone marrow. CHOP and CHOP-E were performed, without any remarkable change in the size of the spleen. However, after infusion of rituximab (375 mg/m2, once weekly for 2 weeks), there was a marked reduction of the spleen size and the number of circulating villous cells. Splenectomy was performed afterwards, followed by 2 cycles of rituximab infusion. The patient is now followed on an outpatient basis without any sign of relapse.     

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.