Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 73-year-old woman was diagnosed with seropositive destructive rheumatoid arthritis in 1981. She was treated with cortisone, chloroquine, and cyclophosphamide (Sendoxan) in 1982 and 1984 and contracted severe neutropenia. After that she only received cortisone. During 1991, again low neutrophilic counts were registered, especially granulocytopenia. At first, B-cell lymphoma was suspected, but later Felty's syndrome was established. The patient was treated with high-dose cortisone with some success and had a few minor septic episodes. In May 1992 she contracted a traumatic wound on the back of the lower leg. Conservative treatment resulted in a worsening of the condition and an increased wound area, most likely related to the neutropenic condition. In mid July the patient was hospitalized. Bacterial isolates yielded mixed gram-negative enteric bacteria from the wound. Parenteral antibiotic treatment was started, followed by oral drugs, rhG-CSF (filgrastim) was given subcutaneously once a day, starting 3 days after admission. This resulted in increased numbers of peripheral granulocytes. The ulcer started to heal and by mid August the patient received a transplant with autologous skin grafting. In mid September the wound was completely healed. It is concluded that the combination of antibiotics, skin transplantation, and G-CSF was necessary for the successful result. Actually, the bacterial growth did not call for antibiotics, but it was considered necessary to cover for staphylococci. No worsening of the underlying arthritis was observed.
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PMID:Successful treatment of chronic wound infection in neutropenia and rheumatoid arthritis with filgrastim (rhG-GSF) 752 58

Type II collagen-induced arthritis (CIA) is a pathologic process mediated, in part, by humoral immune mechanisms. Because many antibody-mediated reactions are neutrophil-dependent, the role of this cell population was examined in passive CIA transferred with anti-type II collagen (CII) antibody. In cyclophosphamide (CY)-induced leukocytopenic rats, swelling and inflammation associated with the arthritic response were significantly reduced. Concomitant administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to leukocytopenic rats for 7 consecutive days from the day of CY injection resulted in the recovery of peripheral blood neutrophils count and the abrogation of the suppression of arthritis with an optimal dose of anti-CII antibody. Further study demonstrated that a prior administration of rhG-CSF to naive rats for five consecutive days resulted in the significant and specific increase of peripheral blood neutrophils count and enhancement of passive arthritis with a suboptimal dose of anti-CII antibody. It was suggested that neutrophils played an important role in the development of passive CIA.
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PMID:The effects of recombinant human granulocyte colony-stimulating factor on passive collagen-induced arthritis transferred with anti-type II collagen antibody. 769 55

Chronic neutropenia associated with collagen vascular disease is seen principally with Felty's syndrome complicating rheumatoid arthritis. Multiple recent reports document the efficacy of both granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in reversing the neutropenia and decreasing the risk of infections in Felty's syndrome. Long-term use of G-CSF appears well tolerated and effective in Felty's syndrome. Of concern, however, have been flares of arthritis and development of leukocytoclastic vasculitis in several patients following the use of colony-stimulating factors (CSFs) in Felty's syndrome. The incidence of these complications of CSF therapy appears to be greater in Felty's syndrome than in other disorders. Future studies will need to address the incidence of these side effects, evaluate strategies to reduce risks, and clarify the optimum use of CFSs in Felty's syndrome.
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PMID:Use of colony-stimulating factors in the treatment of neutropenia associated with collagen vascular disease. 920 36

Felty's syndrome (FS) (rheumatoid arthritis with neutropenia and splenomegaly) has a poor prognosis, largely because of the high risk of severe infection. Granulocyte colony-stimulating factor (G-CSF) is an emerging treatment for chronic neutropenia. We prospectively monitored its use in eight patients with recurrent infections or who required joint surgery. Significant side-effects were documented in five, including nausea, malaise, generalized joint pains, and in one patient, a vasculitic skin rash. In two patients treatment had to be stopped, and in these cases G-CSF had been started at full vial dosage (300 micrograms/ml filgrastim or 263 micrograms/ml lenograstim) alternate days or daily. G-CSF treatment was continued in three patients by restarting at reduced dose, and changing the proprietary formulation. G-CSF raised the neutrophil count, reduced severe infection, and allowed surgery to be performed. A combined clinical and laboratory index suggested that long-term treatment (up to 3.5 years) did not exacerbate the arthritis. Once on established treatment, it may be possible to use smaller weekly doses of G-CSF to maintain the same clinical benefit. One of the three patients whose FS was associated with a large granular T-cell lymphocytosis showed a reduction in this subset of lymphocytes during G-CSF treatment.
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PMID:Treatment of Felty's syndrome with the haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF). 951 12

This review focuses on the various rheumatologic manifestations of hematologic diseases and is based on the English literature published over the past year. Interrelationships between leukemia, lymphoma, POEMS syndrome, multiple myeloma, hemophilia, and rheumatic manifestations are discussed. Other less common associated conditions dealt with include the RS3PE syndrome, large granular lymphocyte syndrome, and interferon-related arthritis. Finally, therapeutic measures, such as bone marrow transplantation and the use of granulocyte colony-stimulating factor, are reviewed.
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PMID:Rheumatologic features of hematologic disorders. 989 32

A 65-year-old woman was admitted to our hospital with arthritis and agranulocytosis. She had given a diagnosis of acute myelogenous leukemia (FAB classification M1) a year ago and treated with 3 cycles of cytarabine and anthracycline or etoposide for 4 months, achieving complete remission state. Her bone marrow aspirate revealed normocellularity with normal karyotype (46, XX [20]) without apparent dysplastic feature at this time. She received autologous peripheral blood stem cell transplantation subsequently after conditioning regimen consisted of granulocyte colony-stimulating factor, busulfan, Ara-C and etoposide. Three months later, she started to manifest low grade fever, polyarthralgia and agranulocytosis and she admitted to our hospital after nine months. Bone marrow aspirate revealed marked hypocellularity with dysplastic features in three series of hematopoietic cells. Arthritis was dramatically improved after administration of prednisolone, but low granulocyte count continued. Bone marrow aspirate revealed karyotypic abnormality with monosomy 7 and we diagnosed her as myelodysplastic syndrome. Chemotherapy-induced myelodysplasia has been reported so far. This case would represent secondary myelodysplastic syndrome after chemotherapy. We could not clarify the etiology for polyarthritis but could be one of the paraneoplastic syndrome. We should note subsequent occurrence of myelodysplasia when planning treatment schedule.
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PMID:[Myelodysplastic syndrome after autologous peripheral blood stem cell transplantation for adult acute myelogenous leukemia]. 1042 26

Since 1996, a number of investigators have carried out phase I-II studies of high-dose immunosuppression with autologous hematopoietic stem cell transplantation (HSCT) in autoimmune diseases. Most of this activity has been in studies of multiple sclerosis (MS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and juvenile idiopathic arthritis (JIA). Supported by animal models of antigen-induced autoimmunity, the rationale of HSCT is to time-shift the clinical autoimmunity to an earlier period, restoring self-tolerance. Even with the considerable experience of more than 200 transplantations since 1996, it is difficult to judge the optimal approach. This difficulty is in part because of the multiplicity of centers and protocols and the variability in patient eligibility and assessment, the extent of T-cell depletion, and the intensity of the preparatory regimens used. Other than that found in RA, treatment-related mortality has been higher than expected: 17% in SSc (with an additional 10% mortality from progressive disease), 13% in SLE, 13% in JIA, and 8% in MS. Protocol changes to improve safety have been instituted. These changes include the avoidance of high-dose rabbit antithymocyte serum in patients who received T-cell-depleted grafts, use of corticosteroids with granulocyte colony-stimulating factor during stem cell mobilization and as prophylaxis for the engraftment syndrome in MS, lung radiation shielding in SSc, and multiple precautions against the macrophage activation syndrome in JIA. Responses to primary and secondary endpoints have been seen, and there is a consensus among investigators and regulatory bodies that the time has come for randomized phase II-III studies. Each disease presents distinct difficulties: in MS, restriction of eligibility to patients with active inflammatory disease; in SSc, formulation of cardiopulmonary eligibility criteria to decrease risk; in SLE, judgment of whether HSCT adds any advantage to high-dose nonmyeloablative immunosuppressive treatment alone; and in RA, enhancement of response durability. All prospective randomized studies in these diseases must address problems in selection of the comparison nontransplantation treatment and appropriate stopping rules, particularly with treatment arms of unequal risk. Parallel trials in Europe and in the United States are in the late stages of design.
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PMID:High-dose immunosuppression and hematopoietic stem cell transplantation in autoimmune disease: clinical review. 1206 60

Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in the medium term rhG-CSF is not associated with an excess of lymphoproliferative disorders. Currently, caution on the long-term safety of the use of rhG-CSF in healthy donor is still warranted but the data so far accumulated on allogeneic PBSC transplants are encouraging both as far as concerns the good short-medium tolerability profile of G-CSF-stimulation of the donor and the potential major efficacy in leukemia patients.
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PMID:The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation. 1241 88

Granulocyte colony-stimulating factor (G-CSF) is a well known regulator of granulopoiesis, but the role of endogenous G-CSF in inflammatory joint disease has not been explored. We studied the response of G-CSF-deficient mice in experimental models of joint inflammation. We show that G-CSF deficiency protects mice from acute and chronic arthritis. Reduced severity was associated with blunted mobilization of granulocytic cells from the bone marrow and less cellular infiltrate and cellular activation in inflamed joints. We also demonstrate that G-CSF blockade in established collagen-induced arthritis in WT mice markedly reduces disease manifestations and is as effective as tumor necrosis factor blockade. Our results reveal a critical role for G-CSF in driving joint inflammation and highlight G-CSF as a potential therapeutic target in inflammatory joint diseases, such as rheumatoid arthritis.
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PMID:Critical role for granulocyte colony-stimulating factor in inflammatory arthritis. 1527 75

Antineutrophil antibodies are well recognized causes of neutropenia, producing both quantitative and qualitative defects in neutrophils and increased risk for infection. In primary autoimmune neutropenia (AIN) of infancy, a moderate to severe neutropenia is the sole abnormality; it is rarely associated with serious infections and exhibits a self-limited course. Chronic idiopathic neutropenia of adults is characterized by occurrence in late childhood or adulthood, greater prevalence among females than among males, and rare spontaneous remission. Secondary AIN is more commonly seen in adults and underlying causes include collagen disorders, drugs, viruses and lymphoproliferative disorders. In most patients with AIN, antibodies recognize antigens located on the IgG Fc receptor type 3b but other target antigens have been recently identified in secondary AIN. Granulocyte colony-stimulating factor is a proven treatment in patients with AIN of all types and is now preferred to other possible therapies.
Arthritis Res Ther 2005
PMID:Primary and secondary autoimmune neutropenia. 1620 50


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