Rheumatoid Arthritis: Rozin A

Rozin A, Schapira D, Braun-Moscovici Y, Nahir AM. · B. Shine Department of Rheumatology, Rambam Medical Center, Haifa, Israel. · Semin Arthritis Rheum. · Pubmed #11590583 No free full text.

Abstract: OBJECTIVES: To review the literature on the immunomodulatory and anti-inflammatory properties of cotrimoxazole (CTX)-a combination of sulfamethoxazole and trimethoprim, to summarize the use of this medication in the treatment of autoimmune diseases, to stimulate and renew the interest of both physicians and researchers in this possible therapy for rheumatoid arthritis (RA), and to inspire further investigation in this field. METHODS: A MEDLINE search of the literature from 1966 until 2000 was performed, and information about the pharmacology of CTX and its use in the therapy of rheumatic diseases was critically reviewed. RESULTS: RA treatment is associated with numerous problems such as lack of efficacy, frequent side effects, and high cost. Analysis of the relevant literature revealed that experience with CTX in the treatment of RA is limited. However, the results of several nonrandomized and evidently forgotten clinical trials and laboratory investigations suggested that CTX might serve as an effective and inexpensive therapy for RA. Several lines of evidence suggested that CTX has nonspecific anti-inflammatory and immunomodulatory properties. Although nausea and vomiting were common reasons for CTX withdrawal, they were noted in only some studies, and no major organ toxicity was observed. CONCLUSIONS: Because of its therapeutic qualities, low cost, and relative nontoxicity, CTX seems to warrant a role in the treatment of RA.

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.

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.

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.

Rozin A, Schapira D, Nachtigel A, Menahem NA. · B Shine Dpt of Rheumatology, Institute of Technology, Haifa, Israel. · Harefuah. · Pubmed #11851101 No free full text.

Abstract: This is a case report of a 21 year old young man who suffers from severe early bilateral hip joint osteoarthrosis. Due to this surprising finding we discuss the differential diagnosis between Kashin-Beck disease, an endemic disease of the patients prior living area (east Siberia) and severe hip joint damage secondary to juvenile rheumatoid arthritis and other diseases.

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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