Felty's Syndrome Research Articles

AB0338 Large Granular Lymphocyte Syndromes Associated with Rheumatoid Arthritis: Report of 6 Cases

BackgroundThe large granular lymphocyte leukemia (LGG) is a rare lymphoproliferative disorder characterized by neutropenia, splenomegaly and infection, which is associated with rheumatoid arthritis (RA) up to 36% of cases. This...

SAT0138 Cumulative Burden of Rheumatoid Arthritis Disease Severity Impacts Cardiovascular Disease Risk

BackgroundRheumatoid arthritis (RA) disease severity is linked to unfavorable cardiovascular disease (CVD) outcomes. Cumulative measures of RA disease burden on CVD have not been well-studied and could be used to...

Giantsplenomegaly in Felty's syndrome

Se presenta caso de mujer de 56 anos de edad que consulta por esplenomegalia gigante y severa bicitopenia, secundaria a artritis reumatoide. El cuadro hematologico revirtio tras esplenectomia.

10. Long-Term Remission of Felty's Syndrome with Rituximab

month history of genital ulceration, recurrent large joint arthritis of the knees and ankles, intermittent abdominal symptoms and severe headaches. A CT angiogram (CTA) revealed two fusiform aneurysms; one arising from the left peri-callosal artery and a second one from a more distant right peri-callosal artery. The appearance of the aneurysms alluded to an inflammatory cause and the diagnosis of Behcet’s was suspected. Due to the position of the aneurysms endovascular and surgical treatment was considered too risky. He was treated medically with 3 days of high dose methylprednisolone followed by prednisolone 40 mg daily. Results: He was readmitted 1 week later with left arm weakness and was found to have two new cortical infarcts in the territories close to the aneurysms. A CTA at this time indicated shrinking of the aneurysms. A further CTA 3 months later confirmed the disappearance of the aneurysms with no new aneurysms detected. Additional investigations to confirm the diagnosis included a CT TAP, which showed thickening of the aorta. A PET scan showed no evidence of active vasculitis. HLA B51 was negative. He is currently being treated with MTX as a steroid-sparing agent following the advice of rheumatology colleagues at the Hammersmith. Additionally, he required renal artery stenting for left renal artery stenosis. Conclusion: This case highlights the rare complication of cerebral aneurysms in BD and the effectiveness of steroid immunosuppression for the treatment of small, unruptured aneurysms. There have been only two reported cases where aneurysms associated with BD have been treated solely with steroids resulting in resolution. In case of rupture surgical or endovascular treatment may be the first choice. Disclosure statement: The authors have declared no conflicts of interest.

Familial CD3+ T large granular lymphocyte leukemia: evidence that genetic predisposition and antigen selection promote clonal cytotoxic T-cell responses

CD3+ T-large granular lymphocyte (T-LGL) proliferations often present with cytopenias and splenomegaly and are linked to autoimmunity, especially rheumatoid arthritis and Felty's syndrome. We report here the intra-family occurrence of T-LGL leukemia in a father and son, both presenting with cytopenias and splenomegaly. Both patients carried the HLA-DRB1*04 allele, strongly associated with rheumatoid arthritis and Felty's syndrome, exhibited distinctive histopathological features suggestive of immune-mediated suppression of hematopoiesis and expressed a remarkably skewed T-cell receptor beta chain gene repertoire with overtime evolution (clonal drift). Immunoinformatics analysis and comparisons with clonotype sequences from various entities revealed (quasi)identities between (i) father and son, and (ii) father or son and patients with autoimmune disorders, T-LGL leukemia or chronic idiopathic neutropenia. Altogether, our results further corroborate antigen selection in the ontogeny of T-LGL leukemia and point to the interplay between genetics and the (micro)environment in shaping the outcome of cytotoxic T cell responses.

Treatment with Rituximab in a Patient with Refractory Felty Syndrome and Low Rheumatoid Arthritis Disease Activity: A Case Report

Felty syndrome (FS) is a rare manifestation in rheumatoid arthritis (RA) characterized by neutropenia and splenomegaly. Treatment for FS is not well established because there has been no randomized controlled study. A few recent reports found rituximab effective in patients with refractory FS. According to those reports, most patients with RA and FS had active arthritis. Here we report a case of a patient with glucocorticoid dependent and disease-modifying anti-rheumatic drugs (DMARDs) refractory FS and quiescent RA who was successfully treated with rituximab.

Diagnosis of Felty’s syndrome, distinguished from hematological neoplasm: A case report

Felty’s syndrome (FS) is characterized by the three conditions of rheumatoid arthritis (RA), neutropenia and splenomegaly, and occurs in few cases of longstanding erosive RA. Discriminating between rare occurrences of autoimmune diseases and malignancies is crucial. The present study describes the case of a 17-year-old female with a two-year history of RA, presenting with an irregular fever, hepatosplenomegaly and enlarged lymph nodes. The antinuclear antibody titer was 1:320, while antibody results for anti-dsDNA, anti-Sm and rheumatoid factor were negative. The clinical presentation was similar to that of lymphoma. However, the fluorodeoxyglucose-positron emission tomography and biopsy examinations of the liver and cervical lymph node did not support the diagnosis of lymphoma. According to the laboratory results and clinical symptoms, the differential diagnosis indicated FS, and immunosuppressive agents were administered. Two weeks later, the patient no longer had a fever, and the transaminase levels were normal, associated with shrinkage of the liver and spleen.

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Introduction: Hydroxychloroquine is a Aminoquinoline derivative which is widely used for treatment of malaria, rheumatoid arthritis and lupus besides many other autoimmune diseases. Though neutropenia is listed as a potential side effect, there is no reported case in the literature. We present a very rare presentation of hydroxychloroquine toxicity. CASE PRESENTATION 36 year old female presented with fever, malaise, chills and a lip rash for 3 days duration.Her past history included eosinophilic fasciitis being treated with methotrexate for 2 years which was stopped due to intolerence 3 weeks ago and she was started on hydroxychloroquine 300mg daily. Investigation revealed WBC 300,absolute neutrophil 0, Hg 13.1, Hct 39.2, platelets 51,000. Hydroxychloroquine was stopped and she was admitted in ICU for septic shock. She was started on Filgrastim and broad spectrum antibiotics for neutropenic fever. Her blood cultures were positive for methicillin sensitive Staphylococcus aureus which was treated with appropriate antibiotics.. On day 4 her count were 21,700 with absolute neutrophil 17,190. Filgrastim was then stopped. White blood count increased up to 44,100. She was afebrile from day 2 and her repeat cultures were negative. She was successfully treated and discharged to home on day 10 of hospital admission. Discussion: Hydroxychloroquine has relative safety profile with 0.73% incidence of neutropenia. Though there are some case reports of its use to treat neutropenia in some condition like Felty's syndrome(1), this is the first reported case of profound neutropenia to the best of our knowledge. This case illustrates the importance of anticipation and early recognition of its potential fatal side effect. REFERENCES: 1 Neutropenia in Felty's syndrome successfully treated with hydroxychloroquine. Mahévas M, Audia S, De Lastours V, Michel M, Bonotte B, Godeau B. Chloroquine cardiomyopathy - a review of the literature.Tönnesmann E, Kandolf R, Lewalter T.Immunopharmacol Immunotoxicol. 2013 Jun;35(3):434-42. doi: 10.3109/08923973.2013.780078. Epub 2013 May 1.12. Efficient and effective screening for hydroxychloroquine toxicity.Marmor MF.Am J Ophthalmol. 2013 Mar;155(3):413-4. doi: 10.1016/j.ajo.2012.10.020.

Acute Thigh Pain in a Patient with Felty's Syndrome: A Case Report

Acute Thigh Pain in a Patient with Felty's Syndrome: A Case Report

Felty's syndrome with hyperthyroidism: a case report and literature review

Felty's syndrome with hyperthyroidism: a case report and literature review

THU0048 Radius 1: Correlation between serious infection events (SIES) and rheumatoid arthritis (RA) disease activity in patients requiring a change in therapy

BackgroundThe RA Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study–1 (RADIUS 1) was a real-world, prospective, 5-year, observational study of 4968 patients (aged ≥18 y) with RA (per 1987 American...

Two Suspected Cases of Immunoglobulin-Mediated Interference Causing Falsely Low Vancomycin Concentrations with the Beckman PETINIA Method

To describe 2 recent cases of suspected immunoglobulin-mediated interference with the Beckman Coulter particle-enhanced turbidimetric inhibition immunoassay (PETINIA) used to measure vancomycin serum or plasma concentrations and to review the existing literature. A 64-year-old woman with a history of multiple immune-related comorbidities received vancomycin for treatment of a prosthetic joint infection growing coagulase-negative Staphylococcus spp. A 33-year-old man with a history of Felty syndrome received vancomycin for the treatment of methicillin-resistant Staphylococcus aureus pneumonia. Both patients had multiple vancomycin trough concentrations determined using the Beckman Coulter PETINIA method and had measured concentrations reported as less than 4 mg/L despite appropriate vancomycin dosing for their size, age, and organ function. The patients' serum was then tested by alternative methods, which reported vancomycin concentrations consistent with those expected with the patients' dosing regimens. Immunoglobulins are well known for interfering with chemistry assays. It is suspected that high levels of immunoglobulins in these 2 patients interfered with the accurate measurement of serum vancomycin concentrations. An objective causality assessment supported the interactions as being definite and probable, respectively. Two other cases of suspected immunoglobulin interference with vancomycin measurement have been reported in the literature when vancomycin concentrations were initially measured using the Beckman Coulter PETINIA method. In vitro studies support the hypothesis that immunoglobulin interference with vancomycin measurement by this method occurs and is a graded phenomenon. These cases suggest a high likelihood of immunoglobulin-mediated interference with the Beckman Coulter PETINIA method, which results in the reporting of falsely low vancomycin serum concentrations. When vancomycin concentrations do not correlate with what would be expected clinically, clinicians should have a high index of suspicion for potential assay interference.

Die Milz bei nicht-malignen hämatologischen Erkrankungen

The spleen functions as a filter of the circulating blood, removing aging or abnormal red blood cells, intraerythrocyte inclusions as well as foreign particals. As the spleen is composed of lymphocytic tissue, circulatory elements and mononuclear phagocytic cells it plays an important role in the nonspecific as well as the specific immune response. Additionally, the spleen serves as a reservoir for circulating blood cells, especially platelet sequestration by the spleen is well do cumented. The spleen produces blood cells during fetal development and in certain haematological disorders such as myelofibrosis. The destruction of red blood cells within the splenic cords releases iron in the circulation, which is recycled and used to manufacture new erythrocytes in the bone marrow. In several non-malignant haematological disorders antibody-coated cells are cleared from the circulation by phagocytic cells of the spleen. This involves erythrocytes in autoimmunhaemolytic anaemias, platelets in immunthrombocytopenia and neutrophils in Felty syndrome. In hereditary spherocytosis the spleen destroys the resulting defective, spherical red cells. In pyruvate kinase deficiency impaired production of adenosine triphosphate leads to destruction of red blood cells in the spleen or in the liver. In sickle cell anaemia the defective erythrocytes cause sludging and thrombosis in small vessels with infarcts for instance in the spleen, which over time can result in autosplenectomy. In thalassaemia major abnormal haemoglobin forms protein precipitates in the red cells with development of a severe hypochromic anaemia with haemolysis and intramedullary inef fective erythropoiesis. Therapeutic splenectomy can be an option in all of these mentioned non-malignant haematological disorders. The rationale and the pathophysiology of its role in thrombotic thrombocytopenic purpura is probably at least well understood. The use of new and effective drugs such as the monoclonal antibody rituximab or thrombopoietin agonists in immunthrombocytopenia as well as the option of a laparoscopic rather than an open splenectomy have changed our view on benefits and risks of splenectomy in recent years. To minimize these risks such as overwhelming postsplenectomy infection or abdominal vein thrombosis, prophylactic vaccination, postoperative thromboembolism prophylaxis and patient education is mandatory.

Felty's syndrome without rheumatoid arthritis?

Felty's syndrome (FS) is characterized by neutropenia and splenomegaly in patients with seropositive (RF+, anti-CCP+) rheumatoid arthritis (RA). As a result of neutropenia, affected persons are increasingly susceptible to infections. In the majority of patients, FS appears in the course of long-standing and well-established RA. Manifestations of FS without clinical but only with laboratory features of RA are extremely rare. We present a case of severe neutropenia and mild splenomegaly in a patient with high titers of RF and anti-CCP. For 4 years, patient's neutropenia remained asymptomatic. The neutropenia reduction to agranulocytosis was followed by successful methotrexate-corticosteroid therapy. Efficacy of the standard anti-RA therapy confirmed autoimmune mechanism of the Felty's neutropenia. The most important lesion from our case is to recognize this condition in the range of autoimmune rheumatic diseases without delay. We reviewed literature with non-articular FS.

A case report on Felty′s syndrome

A 35 years old female came to orthopedic OPD with multiple joint pain since 1 year with history of fever and morning stiffness without any history of trauma and previous infection. On examination there was small joint tenderness involving metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints with splenomegaly. Routine investigation revealed neutropenia and rheumatoid factor (RF) was positive. Patient was diagnosed to be suffering from Felty's syndrome. Treatment was initiated with methotrexate. Overall treatment was tolerated well, except for the development of mild fever, mild arthritis and transient thrombocytopenia. She is currently on methotrexate with reasonable control of her symptoms.

Targeted Therapy with Rituximab in Felty's Syndrome: A Case Report

Felty’s syndrome is a rare, severe extra-articular manifestation of rheumatoid arthritis (RA). There is no standard therapy, and several disease-modifying antirheumatic drugs have been used with varying success. Only very few reports exist in literature on the use of biologicals in this indication and this with a variable efficacy. We report the case of a 53-year-old woman with severe refractory/partly undertreated RA who presented with Felty’s syndrome and pancytopenia, in whom treatment with rituximab led to an marked increase of red blood cells, neutrophils and thrombocytes. In addition, the RA disease activity status improved dramatically and treatment with steroids could be reduced. The current sparse literature on this topic is reviewed.

Autoimmune Manifestations in Large Granular Lymphocyte Leukemia

Large granular lymphocyte (LGL) leukemia features a group of indolent lymphoproliferative diseases that display a strong association with various autoimmune conditions. Notwithstanding, these autoimmune conditions have not been comprehensively characterized or systematized to date. As a result, their clinical implications remain largely unknown. The authors offer a comprehensive review of the existing literature on various autoimmune conditions documented in the course of T-cell LGL (T-LGL) leukemia. Though some of them are thought be secondary to the LGL leukemia, others could be primary and might even play a role in its pathogenesis. A considerable clinico-laboratory overlap between T-LGL leukemia associated with rheumatoid arthritis and Felty's syndrome suggests that they are just different eponyms for the same clinical entity.

Neutrophil activation and B-cell stimulation in the pathogenesis of Felty’s syndrome

Felty's syndrome (FS) is a severe arthritic disorder that features chronic neutrophil activation and progresses to neutropenia and susceptibility to unabated infections. The life‑threatening manifestations of FS have focused the attention of clinical experimenters who have made persistent efforts to find new and effective therapies. This review highlights important milestones in the research on FS and draws attention to recent studies on the antigen specificity of antibodies present in patients' sera. Recent data have indicated that immunoglobulins G (IgGs) in patients with FS bind selectively and specifically to deiminated histones and neutrophil extracellular chromatin traps (NETs). Deimination is the conversion of certain arginine residues in proteins to citrullines by the enzyme peptidylarginine deiminase 4. Earlier observations had indicated that IgGs in FS patients avidly bind to citrullinated peptides. These observations suggest that NETosis, the type of cell death that is defined by the release of NETs, provides autoantigens that stimulate B cell responses in this patient group. This insight parallels recent observations in other autoimmune conditions and lends support to the paradigm that NETosis plays a leading role in the pathogenesis of antiself immune responses.

Large Granular Lymphocyte Leukemia as a Complication of Rheumatoid Arthritis

Large granular lymphocyte leukemia is a rare entity belonging to same spectrum of diseases than Felty's syndrome, which might occur in patients with long-standing rheumatoid arthritis. It is clinically characterized by persistent neutropenia and recurrent bacterial infections associated with the presence in both peripheral blood and bone marrow of clonal expansion of atypic lymphocytes with a cytotoxic T cell phenotype, or less frequently an NK-cell phenotype, as well as splenomegaly. It is more frequently diagnosed in seropositive rheumatoid arthritis, with significant structural damage, extra-articular manifestations and persistently elevated values of ESR, despite them having low inflammatory joint activity. We report the case of a 70-year-old male with a long-standing rheumatoid arthritis, who developed septic shock secondary to prosthetic hip infection by Salmonella spp. He showed persistent neutropenia, and an aberrant monoclonal T cell population was detected in both peripheral blood and bone marrow, consistent with large granular lymphocyte leukemia.

Prevalence of autoimmune manifestations in patients with large granular lymphocytic leukemia: Exploratory analysis of a series of consecutive patients.

6555 Background: Review of literature suggests certain autoimmune abnormalities to accompany LGL leukemia. The present study was set to identify the prevalence of autoimmune phenomena in LGL leukemia patients and compare it with same in general population. Methods: We conducted both retrospective and prospective analyses in a series of consecutive patients (n=11) with LGL leukemia that had been followed in outpatient setting. Median age was 71 years ( ± 14 years). The presence of associated autoimmune disorders in our cohort was compared to the published prevalence of these conditions in general population. Statistical analysis: The obtained values were tested for statistical significance using Fisher’s exact test for small number of observations (95% confidence); a p value < 0.05 was considered significant. Results: A total of 45% patients in our study were diagnosed with autoimmune conditions. Identified autoimmune disorders included rheumatoid arthritis [RA] (n=3), Hashimoto thyroiditis (n=3), Felty syndrome (n=1), aplastic anemia (n=1), pernicious anemia (n=1), and leukocytoclastic vasculitis (n=1). Statistical analysis showed the following significance: Hashimoto thyroiditis (p=0.044), RA (p=0.003), Felty syndrome (p<0.001), aplastic anemia (p<0.001), pernicious anemia (p<0.001), and leukocytoclastic vasculitis (p<0.001). Statistical difference was also noted for autoimmune serologic abnormalities, with ANA positivity present in 63.6% of the cases (p< 0.001) and RF present in 50% of the patients (p=0.005). Conclusions: Nearly half of LGL leukemia patients in our cohort had autoimmune conditions, thus significantly exceeding the overall prevalence in general population. Statistically significant differences were recorded for RA, Hashimoto thyroiditis, Felty syndrome, aplastic anemia, pernicious anemia, leukocytoclastic vasculitis, ANA and RF positive serologies. The prevalence of Hashimoto thyroiditis and ANA positivity in our patient cohort was significantly higher than the one in existing literature. Given the relatively small size of the analyzed cohort, larger studies are expected to confirm our findings.