Rheumatoid Arthritis: Nahir AM

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.

Yigla M, Simsolo C, Goralnik L, Balabir-German A, Nahir AM. · Department of Pulmonary Medicine, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa. · Clin Rheumatol. · Pubmed #12086173 No free full text.

Abstract: Two patients with rheumatoid arthritis and empyematous pleural effusion were treated with repeated drainage and intrapleural corticosteroids. One patient with active joint disease improved within 3 months without sequelae, probably because of the systemic therapy. The other patient, with non-active joint disease, had persistent pleural effusion which resulted in pleural thickening and symptomatic restrictive disturbance. It appears that early intervention intended to prevent the accumulation of empyematous pleural effusion could also prevent pleural thickening and fibrosis. Therapeutic options are discussed.

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.

Dain L, Braun-Moscovici Y, Baum E, Nahir AM, Hoffer E. · B. Shine Department of Rheumatology, Israel. · Clin Exp Rheumatol. · Pubmed #16539817 No free full text.

Abstract: OBJECTIVE: To examine whether the release of superoxide anions from neutrophils of healthy donors was affected when incubated with plasma from infliximab-treated rheumatoid arthritis (RA) patients. METHODS: Fifteen consecutive seropositive RA patients were treated with 3mg/kg infliximab on weeks 0, 2, 6, and 14. Disease activity was assessed by DAS28 score and by IL-6 level. Neutrophils from healthy donors were incubated with plasma drawn before each infliximab treatment. PMA-stimulated superoxide release was measured by the ferricytochrome C reduction method. RESULTS: 53% of the patients had a favorable clinical response. IL-6 levels showed a significant decline at week two, with a gradual increase thereafter. Treatment with infliximab did not change the superoxide production. However, when the group was divided retrospectively to responders (DeltaDAS28 > -1.2) and non-responders (DeltaDAS28 < -1.2), two different patterns were seen, although the pre-treatment levels were similar: Among the responders IL-6 remained low at its 2 weeks level till week 14, while in the non responders IL-6 increased 3 times (P < 0.03) from week 2 to 14. The responders showed mild, but continuous, reduction of superoxide release, while in the non-responders it increased significantly from week 2 on. CONCLUSION: The reduction in IL-6 in RA sera following anti-TNFalpha therapy has little influence on the capacity of these sera to stimulate healthy neutrophils to produce superoxide, suggesting the existence of non-TNFalpha non-IL-6 dependent neutrophil-stimulating mediators in RA sera. The increasing level of IL-6 among the non-responders after initial dramatic decline might represent an escape phenomenon, possibly caused by alternative mediator(s). Clinically, this IL-6 "escape" might be used as a tool for early identification of responders from non-responders.

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.

Nagler RM, Salameh F, Reznick AZ, Livshits V, Nahir AM. · Department of Oral and Maxillofacial Surgery, Rambam Medical Center and the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa. · Rheumatology (Oxford). · Pubmed #12890858 links to  free full text

Abstract: OBJECTIVES: The objective of the present study was to analyse salivary gland and free radical involvement in rheumatoid arthritis (RA). METHODS: Thirty-four consenting RA patients (rheumatoid factor-positive) and 18 healthy controls, matched in age and gender, participated in the study. Plasma and saliva samples were harvested and subjected to compositional analysis and various free radical-related tests. RESULTS: The mean salivary flow rate was lower in the RA patients than in the control group, whereas all plasma and salivary antioxidants were increased. Mean values of plasma malondialdehyde and ceruloplasmin were higher in the RA patients. CONCLUSIONS: The effects of RA on salivary gland flow rates and antioxidant compositional parameters may be of great importance for the further elucidation of the role of free radicals in RA pathogenesis and for its general diagnosis and evaluation. The demonstrated correlation between the altered salivary parameters and the severity of the disease may indicate that evaluation of the salivary status of RA patients is warranted.

Markovits D, Schapira D, Wiener A, Nahir AM. · The B. Shine Department of Rheumatology, Rambam Medical Center, Haifa, 31096 Israel. · Clin Rheumatol. · Pubmed #12605320 No free full text.

Abstract: We report a young male with recent onset of rheumatoid arthritis (RA) in whom the remarkable severity of the disease led to additional investigations. The only significant finding was mediastinal lymphadenopathy, without lung involvement. Biopsy of the mediastinal lymph node revealed pathological findings typical of silicosis. To our knowledge, this is the first report of silicosis apparent solely in the mediastinal lymph node of an RA patient. This suggests that lung involvement is not crucial for the development of silica-related arthritis.

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.

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

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