Rheumatoid Arthritis: Balbir-Gurman A

Braun Y, Balbir-Gurman A. · No affiliation provided · Harefuah. · Pubmed #12476631 No free full text.

Abstract: Spondyloarthropathies are characterized by both axial and peripheral joint involvement, by the association with "other diseases" mainly Psoriasis, Crohn's and Anterior Uveitis and by the high prevalence of HLA B-27. While disease modifying drugs, such as Methotrexate or Sulfasalazine, are only partially effective in controlling peripheral arthritis, the treatment of the axial part remained only symptomatic. The recently introduced anti-TNF-alpha drugs Infliximab (Remicade) and Etanercept (Enbrel) for the treatment of Crohn's disease and Rheumatoid Arthritis has been expended to Spondyloarthropathies with highly promising results. The rationale and the early beneficial results of this new approach in spondyloarthropathies are reviewed.

Balbir-Gurman A, Yigla M, Nahir AM, Braun-Moscovici Y. · B. Shine Department of Rheumatology, Rambam Medical Center, Haifa, Israel. · Semin Arthritis Rheum. · Pubmed #16765714 No free full text.

Abstract: OBJECTIVES: To describe the clinical and laboratory features of rheumatoid pleural effusion (RPE) and the diagnostic and therapeutic approaches to this condition. METHODS: The review is based on a MEDLINE (PubMed) search of the English literature from 1964 to 2005, using the keywords "rheumatoid arthritis" (RA), "pulmonary complication", "pleural effusion", and "empyema". RESULTS: Pleural effusion is common in middle-aged men with RA and positive rheumatoid factor (RF). It has features of an exudate and a high RF titer. Underlying lung pathology is common. Generally RPE is small and resolves spontaneously but symptomatic RPE may require thoracocentesis. Rarely, RPE has features of a sterile empyematous exudate with high lipids and lactate dehydrogenase, and very low glucose and pH levels. This type of effusion eventually leads to fibrothorax and lung restriction. Superimposed infective empyema often complicates RPE. Oral, parenteral, and intrapleural corticosteroids, pleurodesis and decortication, have been used for the treatment of sterile RPE. Infected empyema is treated with drainage and antibiotics. CONCLUSIONS: RPE may evolve into a sterile empyematous exudate with the development of fibrothorax. Symptomatic effusions or suspicion of other causes of exudate (infection, malignancy) require thoracocentesis. The "rheumatoid" nature of the pleural exudate in patients without arthritis mandates a pleural biopsy to exclude tuberculosis or malignancy. The optimal therapy of RPE has yet to be established. The role of cytokines in the course of RPE and the possible usefulness of cytokine blockade in the treatment of this RA complication require further evaluation.

Braun-Moscovici Y, Markovits D, Rozin A, Toledano K, Nahir AM, Balbir-Gurman A. · B Shine Department of Rheumatology, Rambam Medical Health Care Campus, Technion, Haifa, Israel. · Isr Med Assoc J. · Pubmed #18548981 links to  free full text

Abstract: BACKGROUND: Infliximab and etanercept have been included in the Israeli national list of health services since 2002 for rheumatoid arthritis and juvenile idiopathic arthritis, and since 2005 for psoriatic arthritis and ankylosing spondylitis. The regulator (Ministry of Health and health funds) mandates using fixed doses of infliximab as the first drug of choice and prohibits increased dosage. For other indications (e.g., vasculitis), anti-tumor necrosis factor therapy is given on a "compassionate" basis in severe refractory disease. OBJECTIVES: To describe our experience with anti-TNF therapy in a single tertiary referral center in northern Israel and to analyze the impact of the national health policy on the results. METHODS: We reviewed the medical records of patients who received anti-TNF therapy in our institution, and analyzed demographic data, diagnosis, clinical and laboratory features, previous and current therapies, and anti-TNF treatment duration and side effects. RESULTS: Between 2001 and 2006, 200 patients received anti-TNF therapy for rheumatoid arthritis (n = 108), juvenile idiopathic arthritis (n = 11), psoriatic arthritis (n = 37), ankylosing spondylitis (n = 29), adult Still's disease (n = 4), overlap disease (RA and scleroderma or polymyositis, n = 6), temporal arteritis (n = 1), polyarteritis nodosa (n = 1), dermatomyositis (n = 1), amyloidosis secondary to RA (n = 1) and Wegener's granulomatosis (n = 1). Forty percent of RA patients discontinued the first anti-TNF agent due to side effects or insufficient response. Higher sedimentation rate and lower or negative rheumatoid factor predicted better response to therapy among RA patients. AS and PS patients had a better safety and efficacy profile. Severe infections occurred in 2% of patients. All eight patients who presented lung involvement as part of their primary rheumatic disease remained stable or improved. A significant improvement was achieved in all six patients with overlap disease. CONCLUSION: Our daily practice data are generally in agreement with worldwide experience. The 'deviations' might be explained by the local health policy at that time. The impact of health policy and economic and administrative constraints should be taken into account when analyzing cohort daily practice data.

Oren S, Mandelboim M, Braun-Moscovici Y, Paran D, Ablin J, Litinsky I, Comaneshter D, Levartovsky D, Mendelson E, Azar R, Wigler I, Balbir-Gurman A, Caspi D, Elkayam O. · Department of Rheumatology, Tel Aviv Sourasky Medical Centre, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel. · Ann Rheum Dis. · Pubmed #17981914 No free full text.

Abstract: OBJECTIVE: To assess the effect of rituximab on the efficacy and safety of influenza virus vaccine in patients with rheumatoid arthritis (RA). METHODS: The study group comprised patients with RA treated with conventional disease-modifying drugs with or without rituximab. Split-virion inactivated vaccine containing 15 microg haemagglutinin/dose of B/Shanghai/361/02 (SHAN), A/New Caledonian/20/99 (NC) (H1N1) and A/California/7/04 (CAL) (H3N2) was used. Disease activity was assessed by the number of tender and swollen joints, duration of morning stiffness and evaluation of pain on the day of vaccination and 4 weeks later. CD19-positive cell levels were assessed in rituximab-treated patients. Haemagglutination inhibition (HI) antibodies were tested and response was defined as a greater than fourfold rise 4 weeks after vaccination or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated in all subjects. RESULTS: The participants were divided into three groups: RA (n = 29, aged 64 (12) years), rituximab-treated RA (n = 14, aged 53 (15) years) and healthy controls (n = 21, aged 58 (15) years). All baseline protective levels of HI antibodies and GMT were similar. Four weeks after vaccination, there was a significant increase in GMT for NC and CAL antigens in all subjects, but not for the SHAN antigen in the rituximab group. In rituximab-treated patients, the percentage of responders was low for all three antigens tested, achieving statistical significance for the CAL antigen. Measures of disease activity remained unchanged. CONCLUSION: Influenza virus vaccine generated a humoral response in all study patients with RA and controls. Although the response was significantly lower among rituximab-treated patients, treatment with rituximab does not preclude administration of vaccination against influenza.

Braun-Moscovici Y, Markovits D, Zinder O, Schapira D, Rozin A, Ehrenburg M, Dain L, Hoffer E, Nahir AM, Balbir-Gurman A. · B. Shine Department of Rheumatology, Rambam Medical Center, Haifa, Israel. · J Rheumatol. · Pubmed #16511906 No free full text.

Abstract: OBJECTIVE:. The treatment of rheumatoid arthritis (RA) has changed dramatically with the introduction of anti-tumor necrosis factor (TNF) agents. Unfortunately, a subset of patients have partial or no response. No measurements were found to predict the efficacy of this therapy. Anti-cyclic citrullinated protein antibodies (anti-CCP) are highly specific and sensitive for RA, and their titer correlates with erosive disease. We investigated the correlation between the efficacy of infliximab therapy and the titer of anti-CCP. METHODS: Thirty consecutive seropositive patients with RA were treated with infusion of 3 mg/kg infliximab on Weeks 0, 2, 6, and 14. Clinical assessment and blood withdrawal were done before each treatment, i.e., at the minimal concentration of the drug. Disease activity was assessed by DAS28 score and by interleukin 6 (IL-6) level. Anti-CCP titer was measured by a commercial ELISA at Week 0 and Week 14. RESULTS: At baseline, 24 patients were positive for anti-CCP antibodies. In most patients there was a significant correlation between clinical response to therapy and anti-CCP titer. The results were especially noteworthy in those patients who showed a sustained and significant decrease in IL-6 levels through the entire period. CONCLUSION: Anti-CCP titer and IL-6 levels might be early predictors of the efficacy of anti-TNF therapy in patients with RA.

Balbir-Gurman A, Guralnik L, Best LA, Vlodavsky E, Yigla M, Menahem Nahir A, Braun-Moscovici Y. · B. Shine Department of Rheumatology, Rambam Health Care Campus, Haifa, Israel. · J Clin Rheumatol. · Pubmed #18679135 No free full text.

Abstract: Pulmonary nodulosis and sterile pleural exudates are well-known extra-articular manifestations in rheumatoid arthritis patients with a positive rheumatoid factor. In some patients, treatment with methotrexate has been postulated as the trigger of these complications. We report a patient with psoriatic arthropathy, negative RF, negative anticyclic citrulinated peptide antibodies but positive antibodies to cardiolipin who developed massive sterile pleural empyema and multiple cavitary pulmonary nodules during methotrexate treatment. We suggest that awareness of methotrexate-induced lung and pleural complications should be extended to other than rheumatoid arthritis diseases, not necessarily accompanied by rheumatoid factor or anticyclic citrulinated peptide antibodies.

Strand V, Balbir-Gurman A, Pavelka K, Emery P, Li N, Yin M, Lehane PB, Agarwal S. · Division of Immunology, Stanford University, Palo Alto, CA, USA. · Rheumatology (Oxford). · Pubmed #17062648 links to  free full text

Abstract: OBJECTIVES: To evaluate the long-term impact on physical function of a single course of rituximab in rheumatoid factor, seropositive patients with active rheumatoid arthritis (RA) despite ongoing methotrexate treatment. METHODS: A randomized, controlled trial comparing rituximab alone [1,000 mg intravenously (iv) on days 1 and 15, n= 40], or in combination with cyclophosphamide (750 mg iv on days 3 and 7, n= 41) or oral methotrexate (> or =10 mg/week, n= 40) with placebo + methotrexate (> or =10 mg/week, n= 40), resulted in significant reductions in disease activity at weeks 24 and 48. Sustained improvements in physical function and standard effect sizes (SES) for changes in components of ACR and EULAR criteria were evaluated over 2 yrs. RESULTS: More patients receiving rituximab + methotrexate completed a 2-yr follow-up without further treatment than those receiving placebo + methotrexate (45% vs 15%, respectively), rituximab alone (10%) or rituximab + cyclophosphamide (22%). This reflected a higher percentage of patients receiving rituximab + methotrexate reporting improvements in Health Assessment Questionnaire Disability Index > or = minimum clinically important difference at 1 and 2 yrs (68% and 30%, respectively) compared with placebo + methotrexate (28% and 15%), rituximab monotherapy (43% and 10%) or rituximab + cyclophosphamide (39% and 12%). SES were high in all rituximab groups and revealed differing patterns of response over time. CONCLUSION: A single course of rituximab with continuing methotrexate in patients with active RA provided clinically meaningful improvements in physical function over 2 yrs, with lower discontinuation rates and larger SES for improvements in ACR and EULAR criteria components.

Rozin A, Yigla M, Guralnik L, Keidar Z, Vlodavsky E, Rozenbaum M, Nahir AM, Balbir-Gurman A. · The B. Shine Department of Rheumatology, Rambam Medical Center, P.O. Box 9602, Haifa 31096, Israel. · Clin Rheumatol. · Pubmed #16211338 No free full text.

Abstract: BACKGROUND: Leflunomide (LEF) is indicated in adults for the treatment of active rheumatoid arthritis (RA). LEF inhibits dehydroorotate dehydrogenase, a key enzyme of the pyrimidine synthesis in activated lymphocytes. Among rare adverse effects, fatal interstitial lung disease has been recently reported during treatment of RA with LEF in Japan. Clinical trials outside Japan do not suggest that LEF causes an excess of pulmonary adverse effects. Development and increase of peripheral rheumatoid nodules in typical sites of RA patients following LEF therapy has been recently reported. OBJECTIVES: Two cases with new and accelerated development of rheumatoid lung nodulosis during LEF therapy were described in this study. METHODS: LEF treatment was administered to two male patients (77 and 66 years old) with long-standing active seropositive nodular RA with failure of multiple second line drugs and without lung involvement. Clinical and laboratory assessment using the American College of Rheumatology response criteria, chest computed tomography (CT), quantification of serum rheumatoid factor (RF), and monocyte count of peripheral blood along with routine laboratory follow up were performed on both patients before and during therapy. In case 1, a bone scan was performed due to sustained limbs pain. Open lung biopsy was performed in case 1 and core lung biopsy in case 2. RESULTS: Both patients achieved full clinical remission during 2 months of LEF therapy. In case 1, the first complaints were limbs pain after 10 months of treatment associated with intensive bone uptake on a bone scan consistent with hypertrophic pulmonary osteopathy. Productive cough developed after 3 months of the therapy in case 2. Initially, these complaints were not attributed to therapy. New lung disease was present on CT with cherry-like progressive cavitary nodules, predominantly involving the basal segments of the right lung. The first lung lesions were found by CT 13 months (case 1) and 7 months (case 2) after the beginning of therapy and were erroneously related to bronchiectasia in case 2. In both cases, the lung biopsy showed necrosis surrounded by epithelioid mononuclear inflammation with giant cells, consistent with rheumatoid lung node. The time that elapsed between the beginning of the first symptoms to LEF discontinuation was very long: 13 months in case 1 and 24 months in case 2. Discontinuation of LEF therapy was followed by an arrest in growth of lung nodules, resolution of limb pain, and gradual improvement of bone scan. A significant decrease of monocyte count and RF level in peripheral blood was observed during LEF therapy in both cases. CONCLUSION: For the first time, we described rheumatoid lung nodulosis as complication of successful LEF therapy for RA. Hypertrophic pulmonary osteopathy with severe limbs pain and dry cough were the first manifestations of the lung nodulosis. Monocytopenia during LEF therapy is proposed to be involved in pathogenesis of this rare complication of LEF therapy.

Rozin A, Balbir-Gurman A, Schapira D. · B. Shine Department of Rheumatology, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. · Clin Exp Rheumatol. · Pubmed #12747269 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: The seasonal effect on the relapse of rheumatoid arthritis and spondyloarthropathies is still unclear. To assess the seasonal distribution of relapse onset in rheumatoid arthritis (RA) and spondyloarthropathy (SpA) and its association with solar factors. METHODS: The monthly distribution of relapse onsets during the years 1998-2000 was retrospectively chart reviewed in 364 patients. In 1998 a total of 131 patients were studied; 60 with seropositive (sp) RA, 30 with seronegative (sn) RA and 41 with SpA; 113 patients in 1999: 44 with spRA, 38 with snRA and 31 with SpA; 120 patients in 2000: 56 with spRA, 38 with snRA and 26 with SpA. All of them were treated in the Department of Rheumatology, which serves the population of northwestern Israel. Solar activity was analyzed according to the "Solar Terrestrial Activity Report Charts 1998-2000". The Central Israel Bureau of Statistics provided the sun global radiation data. Data was assessed during the summer (April-September) and winter (January-March, October-December). The correlation between the monthly distribution of disease relapses and solar factors was measured (SPSS-10 for WIN). RESULTS: Relapses in spRA patients occurred mostly during the summer months with peak activity during the month of July 2000. Single monthly peaks of spRA relapse onset were noted in January 1998-1999 and April 1998 and for snRA in January 1998 and June 2000, but there were no seasonal differences for spRA, snRA and SpA in 1998-1999 and for snRA and SpA in 2000. Relapses in spRA patients were associated with a summer bias of increased solar activity and global solar radiation in 2000 compared with lower peak solar activity in 1998-1999. Furthermore, in 2000 we found a significant correlation of the spRA monthly relapse count to solar activity (p = 0.005) and global sun radiation (p = 0.048) unlike snRA and SpA. No above-mentioned association and correlation was noted in 1998-1999. We revealed mild negative correlation (p = 0.046) of SpA relapse count only to peak solar flux (PSF) by analysis of data for 1998-2000 as one united group. CONCLUSIONS: Relapses were more frequent during the summer of 2000 (May-June-July) in spRA but not in snRA and SpA. The reasons are still unclear. No seasonal differences were observed in 1998-1999. Enhanced solar activity in summer-2000 compared with 1998-1999 may be inferred to be the proposed cause but coincidence may occur as well. Outbreak in RA and SpA was not registered despite increased peak solar activity in 2000. We observed mild evidence of reciprocal relation between SpA relapsing and solar activity during 1998-2000. Solar and any other possible contributory factors remain still to be elucidated.

Schapira D, Stahl S, Izhak OB, Balbir-Gurman A, Nahir AM. · Department of Rheumatology, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa. · Semin Arthritis Rheum. · Pubmed #10468415 No free full text.

Abstract: OBJECTIVES: To analyze the factors which differentiate chronic tophaceous arthritis from rheumatoid arthritis. METHODS: We describe two cases of chronic gouty arthritis masquerading as rheumatoid arthritis. The characteristic features of each of these two conditions and the diagnostic approach are discussed in light of relevant literature. RESULTS: The correct diagnosis was reached by the combination of accurate history taking (family history of gout, alcoholism, previous diuretic therapy and renal stones), guiding clinical features (subcutaneous tophaceous deposits) and specific radiological (assymetrical erosions with sclerotic margins and overlying edges) and laboratory findings (hyperuricemia and hyperuricosuria). It was confirmed by the identification of monosodium urate (MSU) crystals in the synovial and subcutaneous tissues. CONCLUSIONS: Gout and rheumatoid arthritis rarely coexist. Chronic gouty arthritis may mimic rheumatoid arthritis, and vice-versa. Clinical suspicion supplemented by characteristic laboratory, radiological and histologic findings help at reaching an accurate diagnosis.

Rozin AP, Braun-Moscovici Y, Balbir-Gurman A. · No affiliation provided · Ann Pharmacother. · Pubmed #19033477 No free full text.

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Rozin A, Schapira D, Balbir-Gurman A, Braun-Moscovici Y, Markovits D, Militianu D, Nahir MA. · No affiliation provided · Ann Rheum Dis. · Pubmed #12117691 links to  free full text

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Balbir-Gurman A, Schapira D, Bergman R, Nahir AM. · No affiliation provided · J Rheumatol. · Pubmed #10990261 No free full text.

This publication has no abstract.