[Visceral leishmaniasis mimicking Felty's syndrome in rheumatoid arthritis treated with methotrexate and etanercept]. / Imitation eines Felty-Syndroms durch eine viszerale Leishmaniasis bei rheumatoider Arthritis unter Therapie mit Methotrexat und Etanercept.

Visceral leishmaniasis (VL) is a chronic parasitic disease caused by pathogens of the genus Leishmania, which can mimic numerous diseases. The leading symptoms of VL (splenomegaly, pancytopenia, fever) can be misinterpreted, especially if autoantibodies are detected, and lead to the misdiagnosis of an underlying rheumatic disease (e.g. systemic lupus erythematosus, Felty's syndrome). Proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) play an important role in infection control. In this context, there are increasing reports of VL as an opportunistic infection during treatment with anti-TNF­α agents. A case of VL mimicking Felty's syndrome in a patient with rheumatoid arthritis treated with methotrexate and etanercept is presented.

Hematological Manifestations among Patients with Rheumatic Diseases.

BACKGROUND: Rheumatic diseases have many hematological manifestations. Blood dyscrasias and other hematological abnormalities are sometimes the first sign of rheumatic disease. In addition, novel antirheumatic biological agents may cause cytopenias. SUMMARY: The aim of this review was to discuss cytopenias caused by systemic lupus erythematosus and antirheumatic drugs, Felty's syndrome in rheumatoid arthritis, and autoimmune hemolytic anemia, thrombosis, and thrombotic microangiopathies related to rheumatological conditions such as catastrophic antiphospholipid syndrome and scleroderma renal crisis. Key Message: The differential diagnosis of various hematological disorders should include rheumatic autoimmune diseases among other causes of blood cell and hemostasis abnormalities. It is crucial that hematologists be aware of these presentations so that they are diagnosed and treated in a timely manner.

Tocilizumab treatment in Felty's syndrome.

Felty's syndrome (FS) is a deforming disease, characterized by the triad of rheumatoid arthritis (RA), neutropenia, and splenomegaly. Currently, FS patients are treated mainly with immunosuppressants, such as methotrexate and glucocorticoids, which however are not suitable to some patients and may cause severe side effects. Here we report a clinical FS case that was treated with Tocilizumab (TCZ) successfully. The patient had symmetrical swelling and pain of multiple joints, deformity of elbow joints with obvious morning stiffness. Joint color Doppler ultrasound showed synovial hyperplasia and bone erosion of wrist and proximal interphalangeal joints and CT scan suggested splenomegaly. Further examination showed neutropenia and anemia, a high titer of anti-cyclic citrullinated peptide antibody, rheumatoid factor and anti-nuclear antibodies, positive p-ANCA, and elevated IgA and IgG. After treating with TCZ, the patient has been relieved of clinical symptoms. His spleen has recovered to normal size. The absolute neutrophil count (ANC) tended to be stable, and joint erosion did not deteriorate. We have reviewed the literatures on FS treatment with biological agents and found only a few reports using TNF-α antagonist and rituximab treating FS, but none with TCZ. So, it is the first time to report a successful FS case treated with TCZ. This case suggests that the TCZ may be a new choice for FS treatment, under the condition of closely monitoring the ANC.

Phenotypic variability in a child with Felty's syndrome: a case report.

BACKGROUND: Felty's syndrome (FS) is characterized by the triad of rheumatoid arthritis (RA), splenomegaly and neutropenia. The arthritis is typically severe and virtually always associated with high-titer rheumatoid factor. The presence of persistent neutropenia is generally required to make the diagnosis. Most patients diagnosed with FS are aged 50-70 years and have had RA for more than 10 years. It is rarely seen in patients with juvenile idiopathic arthritis (JIA), with only five cases having been reported throughout the world. CASE PRESENTATION: The present study describes the case of a 14-year-old female with a seven-year history of polyarticular JIA, presenting with splenomegaly, hepatomegaly, cholestasis and thrombocytopenia. However, she occasionally developed neutropenia. Titers of rheumatoid factor and anti-CCP were persistently high, and the antinuclear antibody titer was 1:320, while the antibody results for anti-dsDNA and anti-Sm were negative. Serum levels of IgA, IgG, IgM and IgE were all persistently elevated, and the ratio of CD19+ lymphocytes in the subgroups of lymphocytes was persistently high. The level of complements was normal. No STAT3 and STAT5B mutations were found by next-generation sequencing. The patient did not respond to methotrexate, prednisolone, hydroxychloroquine (HCQ), sulfasalazine and etanercept but was responsive to rituximab. CONCLUSIONS: JIA, thrombocytopenia and splenomegaly are the most common and important features in six children with FS, while persistent neutropenia is not seen in all these patients. No complement deficiency has been found in children with FS so far. Manifestations of FS without neutropenia may be extremely rare. There are differences between adults and children in the clinical and laboratory features of FS.

Zytopenien : Anämie, Leukopenie und Thrombopenie.

Hematological alterations can often be observed during rheumatic diseases. The effects can be clinically severe, ranging from anemia of different grades of severity, through increased risk of hemorrhage due to thrombocytopenia up to severe infections as a result of high-grade leukocytopenia. The clinical sequelae for patients are predominantly determined by the extent of cytopenia. The underlying disease itself can initially be considered as the cause. Examples are anemia as a result of chronic inflammation, antibody-mediated thrombocytopenia as in systemic lupus erythematosus (SLE) or granulocytopenia within the framework of Felty's syndrome. Immunosuppressive treatment also often leads to alterations in the blood constituents. Although some substances, such as cyclophosphamide can suppress all three cell types, there are also selective effects, such as isolated thrombocytopenia under treatment with tocilizumab and JAK inhibitors. The differential diagnostic clarification of cytopenia can be difficult and necessitates a systematic work-up of the course of the disease and the subsequent treatment. The reviews of anemia, leukocytopenia and thrombocytopenia presented here summarize the most important components of the differentiation of hematological alterations in patients with rheumatic diseases.

Felty's Syndrome: A Qualitative Case Study.

Felty's syndrome is a triad of rheumatoid arthritis, splenomegaly, and neutropenia. This rare disorder is difficult to diagnose and produces many complications. The purpose of this descriptive qualitative case study was to provide a comprehensive, context-bound understanding of one patient's struggle with the condition.

[Rituximab for treatment of Felty's syndrome]. / Rituximab zur Therapie des Felty-Syndroms.

Felty's syndrome is a rare variant of severe seropositive rheumatoid arthritis with neutropenia and splenomegaly. It is difficult to treat and associated with a poor prognosis due to the substantial risk of infections. This article presents the case of a patient with refractory disease who responded to rituximab with permanent normalization of neutrophil counts. Repeated infusions were necessary to induce and maintain remission.

Felty syndrome: a case report.

BACKGROUND: Felty syndrome is a rare manifestation of chronic rheumatoid arthritis in which patients develop extraarticular features of hepatosplenomegaly and neutropenia. The typical presentation of Felty syndrome is in Caucasians, females, and patients with long-standing rheumatoid arthritis of 10 or more years. This case report presents a patient with an early-onset and atypical demographic for Felty syndrome. CASE PRESENTATION: Our patient is a 28-year-old African American woman with past medical history of rheumatoid arthritis diagnosed in 2017, asthma, pneumonia, anemia, and mild intellectual disability who was admitted to inpatient care with fever, chills, and right ear pain for 7 days. The patient's mother, also her caregiver, brought the patient to the hospital after symptoms of fever and ear pain failed to improve. Our patient was diagnosed with sepsis secondary to pneumonia and urinary tract infection. She had been admitted twice in the past year, both times with a diagnosis of pneumonia. During this visit in September 2019, it was discovered that the patient had leukopenia and neutropenia. Bone marrow biopsy revealed increased immature mononuclear cells with left shift and rare mature neutrophils. During the hospital course, the patient was provisionally diagnosed with Felty syndrome and treated with adalimumab and hydroxychloroquine for her rheumatoid arthritis. Her sepsis secondary to pneumonia and urinary tract infection was treated with ceftriaxone and doxycycline, which was later switched to cefepime because of positive blood and urine cultures for Pseudomonas aeruginosa. She was discharged with stable vital signs and is continuing to control her rheumatoid arthritis with adalimumab. CONCLUSION: This case report details the clinical course of sepsis secondary to pneumonia and urinary tract infection in the setting of Felty syndrome. Our patient does not fit the conventional profile for presentation given her race, age, and the length of time following diagnosis of rheumatoid arthritis.

Rheumatoid arthritis patients with peripheral blood cell reduction should be evaluated for latent Felty syndrome: A case report.

RATIONALE: Felty syndrome is a rare and life-threatening type of rheumatoid arthritis (RA). PATIENT CONCERNS: A patient with RA had skin rash and subcutaneous hemorrhage, with a significant decrease in blood hemoglobin (Hb), white blood cell count (WBC), and blood platelet count (BPC). DIAGNOSES: The patient had a history of RA, splenomegaly, decreased Hb, WBC, BPC, and normal immunological indexes, combined with a series of bone marrow related tests and genetic tests. INTERVENTIONS: She was given high-doses of glucocorticoids intravenously, followed by oral prednisone and cyclosporine maintenance therapy. OUTCOMES: Her symptoms were resolved within 2 weeks after the start of immunosuppression. After 2 weeks of discharge, the Hb, WBC, BPC basically returned to normal, and prednisone gradually decreased. LESSONS: Felty syndrome is a rare complication of RA. Reductions in Hb, WBC, BPC, and subcutaneous hemorrhage should be considered strongly as the possibility of Felty syndrome. Multi-disciplinary diagnosis and related tests of bone marrow and genes are helpful for diagnosis and correct treatment.

Successful abatacept treatment for Felty's syndrome in a patient with rheumatoid arthritis.

We report the case of a 69-year-old man with a 38-year history of rheumatoid arthritis (RA), who developed Felty's syndrome, successful treatment with abatacept (ABT). He was treated with etanercept 50 mg/w and methotrexate 8 mg/w for the past 5 years. He was suffered from febrile neutropenia 6 months ago. Etanercept and methotrexate was discontinued 3 months ago, however, neutrophil count was not changed. Abdominal ultrasound showed splenomegaly, the diagnosis of Felty's syndrome was made. Granulocyte colony-stimulating factor therapy showed no effect on neutropenia, he was treated with ABT. After ABT therapy, absolute neutrophil count was elevated 234/µL to 1840/µL.

Rituximab is useful in the treatment of Felty's syndrome.

Felty's syndrome is regarded as a severe variant of rheumatoid arthritis (RA) that develops in less than 1% of patients with RA. It consists of a triad of RA, splenomegaly, and leukopenia, which tends to develop after a long course of RA. Treatment of neutropenia is mainly comprised of disease-modifying antirheumatic drugs including methotrexate, hydroxychloroquine, auronofin, penicillamine, glucocorticoids, and granulocyte monocyte colony stimulating factor. Recently, there has been a growing interest in the biologic agent rituximab in the treatment of Felty's syndrome. To our knowledge, only one previous case of rituximab being beneficial in the treatment of Felty's syndrome has been reported. We report the case of a 60-year-old man with Felty's syndrome in whom treatment with rituximab led to a sustained neutrophil response and marked symptomatic improvement in the form of decrease in the size of rheumatoid nodules and better pain control.

Diffuse disseminated candidiasis in a patient with Felty's syndrome: a case report.

Severe granulocytopenia predispose patients with Felty's syndrome to severe infectious diseases. The following report deals with an occurrence of chronic disseminated candidiasis in a patient with Felty's syndrome who presented with prolonged and severe granulocytopenia. To the best of our knowledge this coexistence has never been described before.

Pathogenesis of neutropenia in large granular lymphocyte leukemia and Felty syndrome.

T-cell large granular lymphocyte leukemia (TLGL) is an atypical chronic lymphoproliferative disorder derived from cytotoxic T-cells (CTL). Unlike most forms of leukemia, the pattern of bone marrow infiltration in TLGL may be subtle and the cytopenias are often lineage specific, with neutropenia dominating. Both granulocytic survival and proliferation defects are observed and are mediated by humoral and cell-mediated mechanisms respectively. Splenic production of immune complexes induces a neutrophil survival defect, where as Fas expression by leukemic CTL results in a marrow based proliferation defect. These humoral and cell-mediated pathways induce granulocytic apoptosis through independent intracellular mechanisms which are not mutually exclusive and may be observed concurrently in individual patients with either TLGL or FS. A variety of therapeutic interventions have been utilized in the management of TLGL and Felty syndrome, including methotrexate, cyclosporine A, cyclophosphamide, glucocorticoids, myeloid colony stimulating factors and splenectomy. Their efficacy and mechanisms of action are reviewed.