The utility of therapeutic plasma exchange in Hyperviscosity syndrome associated with juvenile rheumatoid arthritis: A case report.

Hyperviscosity syndrome (HVS) is a life-threatening syndrome caused by high concentrations of large plasma proteins like IgM, rheumatoid factor, and other immune complexes, leading to increased blood viscosity and symptoms such as visual abnormalities, neurological impairment, bleeding diathesis, and thrombosis. While Waldenström's macroglobulinemia accounts for 80% to 90% of cases, HVS may develop in other clinical settings characterized by elevations in plasma proteins. Limited evidence currently exists describing the safety and efficacy of therapeutic plasma exchange (TPE) for the management of HVS secondary to non-neoplastic conditions. We report a case of recurrent HVS associated with juvenile rheumatoid arthritis and Felty syndrome that demonstrated improvement in clinical symptoms following initiation of TPE. These findings suggest that TPE may be utilized as an adjunct treatment option in patients with HVS secondary to autoimmune disorders.

Chronic neutropenia in LGL leukemia and rheumatoid arthritis.

This section reviews the diagnostic criteria and pathogenesis of large granular lymphocyte (LGL) leukemia. There is a particular focus on the overlap of LGL leukemia and rheumatoid arthritis (Felty's syndrome). Current understanding of the mechanisms of neutropenia in these disorders is discussed. Finally, treatment indications and therapeutic recommendations are outlined.

Management of autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus.

Autoimmune neutropenia, caused by neutrophil-specific autoantibodies is a common phenomenon in autoimmune disorders such as Felty's syndrome and systemic lupus erythematosus. Felty's syndrome is associated with neutropenia and splenomegaly in seropositive rheumatoid arthritis which can be severe and with recurrent bacterial infections. Neutropenia is also common in systemic lupus erythematosus and it is included in the current systemic lupus classification criteria. The pathobiology of the autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus is complex, and it could be a major cause of morbidity and mortality due to increased risk of sepsis. Treatment should be individualized on the basis of patient's clinical situation, and prevention or treatment of the infection. Recombinant human granulocyte colony-stimulating factor is a safe and effective therapeutic modality in management of autoimmune neutropenia associated with Felty's syndrome and systemic lupus erythematosus, which stimulates neutrophil production. There is a slight increased risk of exacerbation of the underlying autoimmune disorder, and recombinant human granulocyte colony-stimulating factor dose and frequency should be adjusted at the lowest effective dose.

Rituximabe na síndrome de Felty refratária / Rituximab in the refractory Felty's syndrome

Os autores relatam o caso de uma paciente de 29 anos com diagnóstico de artrite reumatoide soropositiva que com seis meses de evolução desenvolveu granulocitopenia severa e esplenomegalia, embora mantivesse em remissão o quadro articular. Não apresentou resposta à corticoterapia oral e em forma de pulsos, além do metotrexato e leflunomida, tendo apresentado reação adversa ao uso do infliximabe e falta de resposta ao adalimumabe. Diante das infecções de repetição, apesar dos vários esquemas de antibióticos e uso crônico do G-CSF, dos altos títulos de fator reumatoide, dos níveis elevados da VHS e da PCR, utilizou-se o rituximabe no esquema clássico de tratamento da artrite reumatoide. Houve resposta clínica completa com aumento crescente do número de neutrófilos e normalização dos mesmos além da queda dos títulos de fator reumatoide, da VHS e da PCR. Atualmente, a paciente encontra-se em remissão clínica e laboratorial, em uso de prednisona 5 mg/dia e metotrexato 10 mg/semana.

The authors report a case of a 29 year old woman who has seropositive rheumatoid arthritis for six months, and developed severe granulocytopenia and important splenomegaly, however she didnït show any joint inflammation. She did not respond either to pulse or oral steroids, or to oral methotrexate and leflunomide. She also developed an adverse reaction to the use of infliximab and did not respond well to adalimumab. Although she has had repeated infections, despite the various forms of antibiotics and long-term use of G-CSF, with high titers of rheumatoid factor, and high levels of ESR and CRP, the classic Rituximab method for treating rheumatoid arthritis was used. There was a good clinical response with an increase in the number of neutrophils following normalization of them, together with the reduction of rheumatoid factor titers, ESR and CRP. At the moment, the patient is in remission, according to both clinical and laboratory criteria and taking 5mg of prednisone per day and 10mg of methotrexate per week.

Síndrome de Felty: relato de caso e revisão da terapêutica / Felty's syndrome: case report and review of therapeutics

Os autores relatam um caso de artrite reumatóide, com 20 anos de evolução, que desenvolveu neutropenia e esplenomegalia em uso de 20 mg de metotrexato, que persistiu mesmo com sua substituição pela ciclosporina A. Apresentou infecções de orofaringe, pele e trato urinário. Após afastar doenças hematológicas, o diagnóstico foi de síndrome de Felty. Realizou-se o tratamento com antibioticoterapia, fator estimulador de colônia de granulócitos e macrófagos, pulsoterapia com metilprednisolona e leflunomida. Evoluiu inicialmente com melhora clínica e laboratorial. Após 2 meses de uso do leflunomida, foi admitida em pronto-socorro com quadro de sepse, ocorrendo o óbito em poucas horas.

The authors describe the case of a 42 years-old female patient with rheumatoid arthritis with a 20 years of follow-up. The patient was using methotrexate (20 mg/week); she developed neutropenia and splenomegaly that persisted despite changing medication for cyclosporine A. She then developed oropharyngeal, skin and urinary tract infections. After excluding for hematological affections, she was diagnosed as presenting Felty's syndrome. She was started on antibiotics while receiving also granulocyte-macrophage colony stimulating factor, pulsed methylprednisolone, and leflunomide. Two moths after the initiation of leflunomide, she was admitted to an emergency hospital unit with septic shock that resulted in her death in a few hours.

Síndrome de Felty: caso de recidiva após suspensão da medicação de base / Felty's syndrome: relapse after discontinuing the medication

Os autores descrevem o caso de uma paciente de 49 anos de idade, com história de 30 anos de artrite reumatóide. Em 1993 desenvolveu neutropenia persistente e esplenomegalia. O diagnóstico foi síndrome de Felty (SF). O tratamento foi realizado com fator estimulador de colônia de granulócitos e macrófagos (GM-CSF), prednisona e metotrexato (MTX). Após melhora clínica e laboratorial, com valores normais de células sangüíneas, apenas o MTX foi mantido obtendo estabilização da doença. Em fevereiro de 2001, a paciente foi considerada em remissão e o MTX foi suspenso. Após dois meses, a paciente apresentou recidiva. Esse caso demonstra a importância da manutenção do tratamento com metotrexato, mesmo em baixas doses, para controlar a atividade da doença, considerando o aumento da morbidade e mortalidade associado às complicações de neutropenia grave

Treatment of the neutropenia of Felty syndrome.

This review sets out to synthesize and critically evaluate the current reported data regarding therapeutic options for the neutropenia associated with Felty syndrome (Felty neutropenia). A MEDLINE search and bibliographies from recent reviews were used to identify trials and case reports that provided sufficient data to evaluate the effect of various interventions on both the neutropenia and the clinical course of patients with Felty syndrome. Data were obtained on baseline hematologic profiles, bone-marrow biopsies, and patient characteristics; length of follow-up; hematologic and clinical responses to the various interventions; and side-effect profiles. Treatment with hemopoietic growth factors or methotrexate can produce sustained hematologic and clinical responses with an acceptable side-effect profile. Splenectomy produces a long-term hematologic response in 80% of patients. Patients who do not respond hematologically have a higher incidence of non-fatal infections, but a significant minority (46%) do not experience any infections; the incidence of fatal infections is 12%, regardless of whether a hematologic response occurs. Of the patients who had infections prior to surgery, 55% did not experience further infections after splenectomy. Initial treatment of Felty neutropenia should consist of hemopoietic growth factors because of their rapid onset of action and relatively low incidence of side-effects. Splenectomy is a reasonable option if growth factors are ineffective and rapid amelioration of neutropenia is needed. Methotrexate offers a potentially promising alternative for the treatment of both the rheumatologic and the hematologic manifestations of Felty syndrome.

[A case of recurrent bilateral shoulder dislocation in a patient with Felty's syndrome]. / Przypadek obustronnego nawykowego zwichniecia stawu ramiennego u chorej na zespól Felty'ego.

A case of recurrent bilateral shoulder dislocation in patient with Felty disease is presented. Good clinical result has been achieved after surgical treatment inclusive of synovectomy and bone bar implantation into the anterior edge of the scapula followed by appropriate rehabilitation.

[Rheumatoid arthritis, neutropenia and splenomegaly: the Felty syndrome]. / Rheumatoide Arthritis, Neutropenie und Splenomegalie: Felty-Syndrom.

HISTORY AND FINDINGS: A 59-year-old asymptomatic man, first diagnosed to have rheumatoid arthritis 27 years ago, was admitted to hospital because of splenomegaly and neutropenia, first noted 2 years ago. Physical examination confirmed splenomegaly and also revealed pretibial hyperpigmentation, but no evidence of active rheumatoid arthritis. EXAMINATIONS: Biochemical tests showed relative and absolute neutropenia (white blood cell count 2200/microliters; 1% neutrophils), thrombocytopenia and polyclonal hypergammaglobulinaemia. He also had increased erythrocyte sedimentation rate (38/92), a high titre of rheumatic factor (2128 IU/ml) and increased circulating immune-complexes (74%). Thoracic and abdominal computed tomography provided no evidence of malignant tumor. The spleen measured 15 x 7 x 10 cm. Bone-marrow biopsy from the iliac crest revealed abnormal maturation of granulopoiesis and marked lymphoid infiltration. The clinical triad of rheumatoid arthritis, splenomegaly and neutropenia are diagnostic of Felty's syndrome. As the patient was asymptomatic there was no indication for treatment. CONCLUSION: Felty's syndrome is a rare condition demanding considerable effort in differential diagnosis.

A prolonged use of granulocyte colony stimulating factor in Felty's syndrome.

Current treatment for Felty's syndrome, a triad of rheumatoid arthritis, splenomegaly and neutropenia, is often unsuccessful. Felty's syndrome may be related to decreased production of hematopoietic growth factors. We treated a patient with Felty's syndrome, profound neutropenia and a history of multiple complicated hospitalization for severe infections, with granulocyte colony stimulating factor (GCSF) for 18 months. After initiation of GCSF, the patient's neutrophil count has remained in the normal range for 18 months. After 2 easily treated infections at the start of therapy, she had only one episode of cellulitis occurring after 18 months when her GCSF dose was reduced to every 3rd day. She has been infection-free since then on every other day therapy. GCSF may be a cost effective longterm therapy for selected patients with Felty's syndrome and may reduce both patients' morbidity and overall medical costs.

Partial splenic embolization for Felty's syndrome: a 10-year followup.

Partial splenic embolization was performed in a case of Felty's syndrome in 1980. The granulocyte count has since remained normal without serious infections for the 10 years after the procedure. This is the first report of partial splenic embolization in this syndrome. This treatment may have an advantage over splenectomy because the defense mechanisms of the spleen are preserved and overwhelming infections may occur less frequently.

Successful reversal of neutropenia in Felty's syndrome with recombinant granulocyte colony stimulating factor.

We report two patients with Felty's syndrome and chronic skin ulcers treated successfully with recombinant granulocyte colony stimulating factor (GCSF). In both cases granulocytes returned to the normal range within days of starting treatment, and their cutaneous ulcers improved. In one patient granulocytes were maintained at normal levels with a regimen of GCSF 3 micrograms/kg twice weekly for 14 months.

GM-CSF and G-CSF in Felty's syndrome.

The risk of infection is increased in patients with Felty's syndrome, neutropenia being one of the main reasons for the susceptibility to infection. We report the case of a 56-year-old patient with Felty's syndrome in whom successive therapy with GM-CSF, splenectomy, and G-CSF was tried because of recurrent severe infections. Therapy with GM-CSF and G-CSF resulted in improvement of neutropenia and in successful treatment of cutaneous and pulmonary infections.

[Felty's syndrome: retrospective study of 12 cases]. / Syndrome de Felty: étude rétrospective de 12 cas.

A retrospective study of twelve cases of Felty's syndrome was performed. The main points of this syndrome (clinical presentation, physiopathology, complications, treatment) are described.

Felty's and pseudo-Felty's syndromes.

Felty's syndrome, consisting of rheumatoid arthritis, leukopenia, and splenomegaly, has been recognized as a distinct clinical entity for more than 60 years. Clinical and laboratory manifestations of the condition are reviewed. The major sources of morbidity and mortality remain recurrent local and systemic infections. Immunogenetic analysis shows a strong association with HLA-DR4, in addition to DQ beta 3b and C4B null allele. Potential mechanisms of neutropenia are contrasted, including impaired granulopoiesis and neutrophil-immune complex interactions. Lithium carbonate and splenectomy may have a role in the treatment of fulminant disease. Maintenance therapy should be directed at control of the underlying inflammatory arthropathy. A syndrome of proliferation of large granular lymphocytes and neutropenia, associated with rheumatoid arthritis in 23% to 39% of cases, has been described recently. Cases of "pseudo-Felty's" syndrome are often confused with traditional Felty's syndrome, which has twice the prevalence. The clinical and laboratory distinctions between these two conditions are elaborated.