Alexandra Balbir-Gurman

Rambam Medical Center, H̱efa, Haifa, Israel

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Publications (90)287.27 Total impact

  • R. Elimelech · Y. Mayer · Y. Braun-moscovici · E.E. Machtei · A. Balbir-gurman ·
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    ABSTRACT: Background: Systemic sclerosis (SSc) is a chronic disease with prominent vasculopathy, inflammation, production of autoantibodies, and tissue fibrosis. Periodontitis is a chronic inflammatory oral condition manifesting as microbial infection, inflammation and destruction of the alveolar bone. In both conditions tumor necrosis factor-alpha (TNFα) and other proinflammatory cytokines play an important role in pathogenesis. Objectives: To assess the periodontal status in SSc patients and compare these parameters to TNFα level in gingival crevicular fluid (GCF) of SSc patients and healthy controls. Methods: Twenty SSc patients and 20 controls underwent periodontal examination, including probing depth (PD), plaque index (PI), gingival index (GI), bleeding on probing (BOP), and measurement of TNFα levels in collected GCF. Results: SSc patients had a greater PD (3.74 ± 0.32 mm vs. 3.35 ± 0.31 mm, P > 0.003), GI (1.53 ± 0.34 vs. 1.12 ± 0.54, P > 0.049), and non-significantly higher BOP than controls. TNFα levels in GCF were higher in SSc patients (1.63 ± 0.36 vs. 1.15 ± 0.34 pg/ml, P = 0.001). Periodontitis parameters correlated with several SS c variables; PI in particular was higher in patients with longer disease duration, sclerodactyly, more severe skin involvement, and SSc activity score. Conclusions: Patients with SSc have higher indices of periodontal inflammation and higher TNFα level in GCF than did healthy individuals. These changes probably reflect the complexity of factors that influence oral health in SSc. Common pathologic pathways may be responsible for the association between SSc and periodontitis, which requires further study.
  • Yolanda Braun-Moscovici · Marius Braun · Dinesh Khanna · Alexandra Balbir-Gurman · Daniel E Furst ·
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    ABSTRACT: Small intestinal bacterial overgrowth (SIBO) plays a major role in the pathogenesis of malabsorption in SSc patients and is a source of great morbidity and even mortality, in those patients. This manuscript reviews which tests are valid and should be used in SSc when evaluating SIBO. We performed systematic literature searches in PubMed, Embase and the Cochrane library from 1966 up to November 2014 for English language, published articles examining bacterial overgrowth in SSc (e.g. malabsorption tests, breath tests, xylose test, etc). Articles obtained from these searches were reviewed for additional references. The validity of the tests was evaluated according to the OMERACT principles of truth, discrimination and feasibility. From a total of 65 titles, 22 articles were reviewed and 20 were ultimately extracted to examine the validity of tests for GI morphology, bacterial overgrowth and malabsorption in SSc. Only 1 test (hydrogen and methane breath tests) is fully validated. Four tests are partially validated, including jejunal cultures, xylose, lactulose tests, and 72 hours fecal fat test. Only 1 of a total of 5 GI tests of bacterial overgrowth (see above) is fully validated in SSc. For clinical trials, fully validated tests are preferred, although some investigators use partially validated tests (4 tests). Further validation of GI tests in SSc is needed.
    Clinical and experimental rheumatology 07/2015; 33 Suppl 91(4):117-122. · 2.72 Impact Factor
  • Y. Braun-Moscovici · M. Braun · D. Markovits · A. Balbir-Gurman ·
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    ABSTRACT: Background Hypocomplementemia was previously reported in patients (pts) with rheumatoid arthritis (RA) treated with tocilizumab (TCZ). Decreased complement (C3,C4) production was suggested as a possible mechanism. The long-term consequences concerning serious bacterial infections or autoimmune disorders (AID) have not been reported. Objectives To assess the long-term outcome of RA pts treated with TCZ who developed hypocomplementemia regarding serious bacterial infections or AID. Methods The charts of RA pts treated with TCZ at our center were reviewed retrospectively. Data regarding pts' age, gender, disease duration, presence of rheumatoid factor (RF), antibodies to citrullinated peptide (ACPA), and nuclear antigens (ANA), previous and concomitant non-biological DMARDs, previous biological DMARDs, and TCZ treatment duration; laboratory parameters including leucocytes and thrombocytes count, liver enzymes, C3 and C4 levels at baseline and during TCZ treatment; episodes of infections, allergic reactions, and AID were captured and analyzed. Results Thirty five pts out of 85 RA pts treated with TCZ, at our center, had serial measurements of serum complement concentration. Fourteen pts (mean age 58.3 years, mean disease duration 8.6 years) developed low C4 levels (9 had also low C3). Mean TCZ treatment period was 4.6 years (range 1-10 years). All patients had normal complement levels at baseline. Seven pts developed persistent leukopenia, 3 pts had persistent thrombocytopenia, 3 pts developed liver enzymes elevation. No serious bacterial infections or new onset AID occurred during follow up. One patient developed a severe allergic reaction. Persistent leukopenia was observed only in 2 out of 21 pts with normal complement levels, as opposed to 5 out of 14 pts with hypocomplementemia. No patients with normal complement levels developed thrombocytopenia. No significant differences regarding previous biologic or concomitant DMARD's treatment were found between the 2 groups of pts. Conclusions Long-term follow up of RA pts treated with TCZ who developed hypocomplementemia did not reveal an increased rate of serious bacterial infections or AID. Persistent leukopenia and thrombocytopenia were frequent in these pts; the relationship to hypocomplementemia needs to be further elucidated. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):734.2-734. DOI:10.1136/annrheumdis-2015-eular.5953 · 10.38 Impact Factor
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    ABSTRACT: Objectives To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. Methods Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. Results 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; −24.0±5.2% vs −7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs −7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases. Conclusions The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.
    Annals of the Rheumatic Diseases 06/2015; 74(6):1188-1194. DOI:10.1136/annrheumdis-2013-204522 · 10.38 Impact Factor
  • O. Elkayam · M. Lidar · T. Reitblat · A. Balbir-Gurman · R. Almog ·

    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):326.2-326. DOI:10.1136/annrheumdis-2015-eular.5437 · 10.38 Impact Factor

  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):88.1-88. DOI:10.1136/annrheumdis-2015-eular.1728 · 10.38 Impact Factor
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    ABSTRACT: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12-24 months in most reports. To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up. We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1,4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed. Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0-4 and 4-7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G). In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.
    The Israel Medical Association journal: IMAJ 03/2015; 17(3):150-6. · 0.90 Impact Factor
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    Alexander P Rozin · Kohava Toledano · Amir Dagan · Alexandra Balbir-Gurman ·
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    ABSTRACT: Background The aim of this study was to measure glenohumeral joint (GHJ) parameters via the anterior access through ultrasound and to compare to data from posterior and inferior accesses. Material/Methods Twenty healthy controls (M: F=15: 5, aged 45.1±11.2 years) and 16 patients (M: F=5: 11, aged 54.6±14.7 years) with active rheumatoid arthritis (RA) (DAS 28 4.6±1.2) were investigated (SonoSite-Titan). To make the GHJ visible on the anterior access, we used the original GHJ opening maneuver. The GHJ width was measured for every transducer position at 2 points. The positions were: posterior transversal, inferior longitudinal, anterior longitudinal along the articular line, anterior transversal upper, middle and lower. The joint width included thickness of cartilage plus synovial fluid/pannus. Rotator interval (RI) width and height (upper biceps channel) were measured. Results Our normal GHJ values by posterior and inferior accesses were within previously estimated values (<2 mm and <3 mm, respectively). We acquired the first values of GHJ width from the anterior access. The last were within a range of 0.7–1.7 mm for healthy controls. Patients with RA showed significantly enlarged joint cavities. RI was not inflamed. Posterior and inferior data of GHJ width were significantly correlated (p=0.01). The data did not correlate with anterior values (p=+0.44, p=−0.56). Synovitis was much more prominent in posterior, upper anterior transversal, and anterior longitudinal accesses. Conclusions The GHJ may be visualized by anterior access using a special maneuver. Synovitis in the anterior region of the GHJ may develop at an independent rate. Anterior GHJ sonography may be complementary to the classic access.
    Medical science monitor: international medical journal of experimental and clinical research 02/2015; 21:533-41. DOI:10.12659/MSM.892520 · 1.43 Impact Factor
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    Zahava Vadasz · Regina Peri · Nasren Eiza · Gleb Slobodin · Alexandra Balbir-Gurman · Elias Toubi ·
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    ABSTRACT: B regulatory cells (Bregs) belong to a subgroup of activated B cells tasked with maintaining self-tolerance and preventing autoimmunity. While sharing similar regulatory mechanisms such as IL-10 dependency, they also defer in exhibiting their suppressive effects by expressing Fas-Ligand, TGF-beta, and PDL-1. In this study we show, for the first time, the expansion of CD25 high FoxP3 high Bregs in systemic lupus erythematosus (SLE) patients compared to healthy individuals (18.5 ± 3.052% versus 11.0 ± 1.654%, p < 0.001 , resp.). This expansion was also shown to correlate with SLE disease activity ( r = 0.75 ). In addition, CD25 high FoxP3 high Bregs were also IL-10 high expressing and further expanded when stimulated with semaphorin 3A. In sum we show that CD25 high FoxP3 high are an additional subtype of Bregs, involved in regulating SLE disease activity. Being IL-10 expressing, we may assume that they are one of the sources of increased serum IL-10 in SLE patients. Further studies are required in order to assess the relation between high serum IL-10 and CD25 high FoxP3 high Breg cells.
    Journal of Immunology Research 01/2015; 2015(4):1-6. DOI:10.1155/2015/254245 · 2.93 Impact Factor
  • Alexandra Balbir-Gurman · Yolanda Braun-Moscovici ·

    Infection and Autoimmunity, 01/2015: pages 735-744; , ISBN: 9780444632692
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    ABSTRACT: A 19-year old previously healthy man developed the adult-onset Still's disease (AOSD) with high ferritin levels. Corticosteroids induced clinical remission with resolution of fever, arthritis, and rash. While tapering corticosteroids, the patient developed severe liver enzymes elevation, very high ferritin levels and, subsequently, acute liver failure. After other causes of liver disease (infections, metabolic, autoimmune hepatitis, lymphoma, and hemophagocytosis) were excluded, severe hepatitis was attributed to AOSD itself. Cyclosporine induced rapid normalization of liver enzymes and reduction in ferritin levels. Severe hepatitis and very high ferritin levels could be the only manifestation of disease activity in AOSD; therefore, monitoring of liver enzymes and ferritin levels is recommended even after resolution of the clinical symptoms of AOSD. Prompt initiation of cyclosporine can improve liver function and prevent progression to liver failure.
    Clinical Rheumatology 11/2014; DOI:10.1007/s10067-014-2829-2 · 1.70 Impact Factor
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    ABSTRACT: Objectives: Infusions of aminobisphonates (ABP) activate Vγ9δ2T cells in vivo and induce an acute inflammatory response in 30% of patients treated for osteoporosis. Following the observation of digital thrombosis in a systemic sclerosis (SSc) patient after treatment with an intravenous ABP, zoledronate (Zol), we evaluated whether patient and control peripheral blood (PB) mononuclear cell (MC, PBMC) acquire a prothrombotic phenotype in response to Zol. Results: Vγ9δ2T cells of both patients and healthy donors (HD) upregulated the CD69 activation antigen and secreted tumor necrosis factor (TNF)α in response to Zol in vitro. In addition, exposure to either Zol or lipopolysaccharide (LPS), or to both additively, induced expression of the highly procoagulant, tissue factor (TF)-1 on CD14+ monocytes. Importantly, only Zol-induced TF-1 was blocked by a monoclonal antibody to TNFα. Interestingly, we found that SSc, but not HD, Vδ1+ T cells were concurrently activated by Zol to produce interleukin (IL)-4. Addition of plasma from the blood of the SSc patient who developed critical digital ischemia after infusion of Zol, but neither plasma from a second patient with no adverse clinical response to Zol infusion nor of a HD, strongly enhanced Zol-induced monocyte TF-1, which could still be blocked by anti-TNFα. Conclusion: Aminobisphonates induced secretion of TNFα by Vγ9δ2+ T cells may lead to TNFα-dependent induction of procoagulant TF-1 induction on monocytes. In certain clinical settings, e.g., SSc, TF-1+ monocytes could play a role in triggering clinically relevant thrombosis.
    Frontiers in Immunology 09/2014; 5:414. DOI:10.3389/fimmu.2014.00414
  • Mohammad Ebrahim Naffaa · Rema Bishara · Yolanda Braun-Moscovici · Alexandra Balbir-Gurman ·
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    ABSTRACT: A 44-year-old woman diagnosed with dermatomyositis 5 years ago based on progressive proximal muscle weakness, elevated creatine kinase, typical findings on electromyography and muscle biopsy. Despite the treatment, in contrast to improvement in her muscle symptoms, the heliotrope rash of her eyelids persisted. After several years, the patient developed multiple limited skin retraction lesions with hyperpigmentation on both lower limbs. Palpation of these lesions revealed dry, cold and very firm skin on both thighs and calves, particularly in the distal areas. X-ray and ultrasound imaging of the calves showed multiple subcutaneous calcifications in the distal muscles.
    Case Reports 08/2014; 2014(aug01 1). DOI:10.1136/bcr-2014-204521
  • Irena Litinsky · Alexandra Balbir-Gurman · Jonathan Wollman · Uri Arad · Daphna Paran · Dan Caspi · Ori Elkayam ·
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    ABSTRACT: The objective of the study was to combine ultrasonographic (US) with clinical findings for comparing the effect of adalimumab (ADA) to methotrexate (MTX) on the thickness of tendons and enthesis in psoriatic arthritis (PsA) patients. Forty-three consecutive PsA patients were examined at baseline and after 6 and 12 weeks of treatment with ADA or MTX. The US assessment included thickness measurement of the extensor (ET) and flexor tendons (FT) of the second and third finger of both hands, plantar aponeurosis (PA) and the Achilles tendon (AT) bilaterally. Disease activity (DA) was assessed by the number of tender (TJ) and swollen joints (SJ), the number of inflamed enthesis (IE), pain assessment (PAI), and patient (PDAI) and physician (PHDAI) disease activity evaluations by visual activity score (VAS). Nineteen patients received MTX and 24 patients received ADA. All DA parameters improved in both groups. A decrease in thickness of tendons and enthesis was observed only in the ADA group, reaching a level of significance for the left AT (p = 0.01), left PA (p = 0.007), the second left FT (p = 0.04) and the third ET (p = 0.04). ADA patients showed a trend towards a better response to treatment compared to MTX patients that reach significance at week 6 of treatment for the thickness of left AT (p = 0.04), left PA (p = 0.03), the number of TJ (p = 0.0136), PAI (p = 0.0028), and PDAI (p = 0.029). ADA treatment for PsA compared to MTX significantly improved signs of DA and several US parameters. US assessment of enthesis can be an additional useful tool in the monitoring of psoriatic enthesopathy.
    Clinical Rheumatology 07/2014; DOI:10.1007/s10067-014-2753-5 · 1.70 Impact Factor
  • A. P. Rozin · K. Toledano · A. Dagan · A. Balbir-Gurman ·
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    ABSTRACT: Background US scan was shown to be effective and useful for investigation of gleno-humeral joint (GHJ) synovitis by posterior and axilar (inferior) access (1,2). Synovial fluid in the subacromial bursa and biceps tendon is also associated with GHJ inflammation (3). Anterior access for GHJ assessment has not been investigated. Rotator interval (RI) is the intra-articular triangular space in the upper anterior part of the biceps bed between supraspinatus (SST) and subscapularis (SSC) tendons. The RI is covered with the GHJ capsule and reflects articular processes. Objectives To measure GHJ parameters and rotator interval from anterior access and to compare to data from posterior and inferior access. Methods Twenty healthy controls (M:F=15:5, age of 45.1±11.2) and 16 patients (M:F=5:11, age of 54.6±14.7) with active rheumatoid arthritis (RA) (DAS28 4.6±1.2) were investigated (Sonosite-Titan, linear 5-10 MHz probe 9L38). In order to make GHJ visible on anterior access we used the original GHJ opening maneuver: supine body position, the adducted to the body elbow and flexed 90 degree on the bed, maximal external shoulder rotation (forearm on the bed). Three structural points are essential for anterior GHJ visualization: 1.A round hyperecoic humeral head; 2. GHJ anecoic cartilage +/- fluid (synovitis); 3. subcscapular tendon situated forward to the GHJ cartilage. The GHJ width was measured for every transducer position at two points. The positions were as follow: posterior transversal, inferior longitudinal, anterior longitudinal along the articular line, anterior transfersal upper, middle and lower. The joint width included thickness of cartilage + synovial fluid/pannus. RI width (SST - SSC) and height (upper biceps channel) were measured. Results See Table 1. Our normal GHJ values by posterior and inferior access were within previously estimated range (posterior GHJ width <2.0mm, inferior <3.0mm) (1,2). We acquired the first values of GHJ width from anterior access. The last were within a range of <1.5-1.7mm for healthy controls. Patients with RA showed significantly enlarged joint cavity in posterior, inferior and anterior access. RI was not inflamed. Posterior and inferior data of GHJ width correlated significantly (p=0.01). The data did not correlate with anterior values (p=0.44, 0.56). Synovitis was much more prominent in posterior, upper anterior transversal and anterior longitudinal transducer positions. Conclusions The GHJ may be visualized by anterior access using a special maneuver. Synovitis in the anterior region of GHJ may develop at an independent rate. Anterior GHJ sonography may be complimentary to the classic access. References Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2010
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):1112-1112. DOI:10.1136/annrheumdis-2014-eular.2010 · 10.38 Impact Factor
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    ABSTRACT: Background Musculoskeletal manifestations occur in 20-50% of patients (pts) with inflammatory bowel disease (IBD) and they have an impact on the clinical course and therapeutic approach. Objectives To summarize the rheumatologic manifestations of IBD pts referred to the rheumatology service in a tertiary referral center and to assess the impact of gastro-rheumatologic inter-disciplinary clinic on patient management. Methods Medical records of 100 consecutive IBD pts referred to rheumatology unit and the inter-disciplinary clinic were retrospectively reviewed. Data regarding age, gender, diagnosis, disease duration, clinical and laboratory features, previous and current therapy were entered into a database and analyzed. The statistical methods used included descriptive statistics, T test, Spearman's correlation and multiple logistic regression analysis. Results Seventy pts suffered of Crohn's disease, 29 of ulcerative colitis, and 1 patient of celiac disease. The mean (median) age was 43 (41.5) years, 68 pts were females, the mean (median) disease duration 7.7 (5) years, range 0-40 years. The referrals were for joint pain (73%), back pain (15%), myalgia (3%), fever (2%), and miscellaneous (7%). Spondyloarthropathy was diagnosed in 56 out of 88 pts referred for joint or back pain (35 pts with peripheral arthritis, 13 pts with axial involvement - symptomatic sacroiliitis or spondylitis, confirmed by imaging and 8 pts with enthesopathies). Hypermobility was found in 18 pts referred for joint pain. The other “musculoskeletal” entities included avascular necrosis of hips (2pts), Takayasu arteritis (1patient), IBD related myositis (1patient), steroid-induced myopathy (2pts), systemic lupus erythematosus (1patient), pseudogout (1patient), insufficiency fractures (1patient) osteoarthritis (2pts).Seventeen pts developed chronic peripheral arthritis which did not correlate to IBD activity and did not consistently respond to IBD-targeted immunomodulatory treatment, including anti-TNF agents, but responded to non anti-TNF biologicals. Nine pts had psoriasis or familial history of psoriasis; all of them developed chronic arthropathy (peripheral or axial). The assessment of the patients at the inter-disciplinary clinic had an important impact on the management in almost 70% of cases referred. Conclusions An accurate assessment of joint inflammation in the context of IBD activity may lead to changes in the use of disease modifying drugs or biological agents. Not every joint or back pain in IBD pts is arthritis or spondyloarthropathy. The treatment of IBD pts with chronic arthritis in whom the IBD is silent should be focused on articular inflammation. We suggest that multidisciplinary clinic might have an important role in correctly diagnosing and treating rheumatologic manifestations in IBD pts. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3629
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):439-439. DOI:10.1136/annrheumdis-2014-eular.3629 · 10.38 Impact Factor
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    ABSTRACT: Background The gastrointestinal tract is involved in nearly all patients with systemic sclerosis (SSc) and is a source of significant morbidity and even mortality. Objectives To assess whether there is correlation between upper gastrointestinal (UGI) endoscopy findings and mortality in SSc patients. Methods The records of 256 SSc patients seen in our rheumathologic clinic between 2003-2013 were reviewed. 140 patients who had at least one detailed upper endoscopy report and at least 6 months follow-up were included in the study. Patient data included demographics, type of SSc, disease duration, modified Rodnan skin score (mRSS), lung, cardiac, renal or musculoskeletal involvement, hemoglobin at endoscopy and type of antibodies. Endoscopic findings that were included in the analysis were esophagitis, ulcerations, tumors, gastric antral vascular ectasia (GAVE), gastric erosions, submucosal hemorrhages and lumenal blood. The statistical methods used included descriptive statistics, T test, bivariable analysis, cox regression analysis Results Forty seven patients (16 diffuse SSc) had evidence of GAVE or antral erosions and hemorrhage. The mortality rate in this group, during the follow up was 37% vs. 25% in the group of 93 (39 diffuse) SSc patients without GAVE or UGI bleeding (p=0.001). There were no statistical differences between the groups regarding mean ages (55) or Hb (10.87 in the group with the UGI bleeding vs 11.77). The mean mRSS score was higher in the group with UGI bleeding 8 vs.5.6 (p=0.019). Mean (median) disease duration was 6.9 (4.5) years in the group with UGI bleeding vs 10.4 (10) (p<0.001). Esophagitis was found in 90% of patients, despite use of PPI. Co-morbidity of myositis had a negative impact on survival. The mortality hazard ratio (95% CI) for UGI bleeding, myositis and interstitial lung disease were 5.9 (2.7-13.2), 4.9 (2-12.4) and 2.7 (1.3-5.8) respectively. Conclusions A diagnosis of GAVE or UGI bleeding on upper endoscopy was associated with significantly higher mortality. In our cohort of SSc patients, myositis was associated also with increased mortality. The long-term survival of patients with GAVE/UGI bleeding was similar to the patients with myositis that were free of such GI complications. The patients with both myositis and GI bleeding had a very poor prognosis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3613
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):571-572. DOI:10.1136/annrheumdis-2014-eular.3613 · 10.38 Impact Factor
  • Abu Shakra M · Zisman D · Levy Y · Balbir-Gurman A · Amital H · Langevitz P · Tishler ·

    Annual Meeting of The Israeli Society of Rheumatology, Haifa; 05/2014
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    ABSTRACT: Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of normal and malignant B lymphocytes. Its use in autoimmune conditions is rapidly expanding. Late-onset neutropenia (LON) is a well-recognized side effect of rituximab therapy in lymphoma patients. Only a small number of cases of LON have been reported in patients with autoimmune disorders. The aim of this work is to review cases in Israel and to compare them to published cases in the literature thus adding to the body of knowledge regarding this unusual phenomenon. Members of the Israeli Rheumatology Association were encountered by e-mail, requesting reports of cases of LON after therapy with rituximab. Submitted cases were reviewed, with demographics and clinical data collated and tabled. Current cases were compared to previously published rheumatology cases. Twelve episodes of LON following rituximab therapy were reported. All patients were female with an average age of 50 years (range 22-78). LON occurred at an average of 155 days after therapy (range 71-330). The average leukocyte count was1,456 white cells, with an average of 413 neutrophils (range 0-1,170 neutrophils). Three of the patients underwent bone marrow biopsies which showed white cell line maturation arrest with an increased number of lymphocytes. No blasts were seen. Our results add support to the growing evidence that this adverse event usually follows a benign course and is not an absolute contraindication for repeat treatment if required in the future. However, vigilance is recommended with routine periodic blood counts, especially 5 months following rituximab administration when the risk is expected to be the highest.
    Clinical Rheumatology 03/2014; 33(9). DOI:10.1007/s10067-014-2562-x · 1.77 Impact Factor
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    ABSTRACT: Background In patients (pts) with RA and other autoimmune diseases the immunogenicity during infliximab (INF) or adalimumab (ADA) therapy lead to the r loss of response. Increasing the drug dose or shortening the re-treatment intervals has economical implications. Switching to another biological agent may be suitable. High levels of anti-INF or anti ADA antibodies (Ab) is accompanied by significant reduction in serum drug concentrations. Objectives To assess the input of measuring serum INF and ADA levels and levels of anti-INF-Ab and anti-ADA-Ab in the management of pts with RA and other autoimmune diseases trated with these drugs. Methods Trough serum levels of INF and ADA and anti-INF-Ab and anti-ADA-Ab were measured by ELISA. Anti-INF-Ab were identified by anti-human lambda chain Ab in order to minimize the interference of serum INF. Treated pts were classified into responders and non-responders based on disease activity. Statistics: descriptive statistics, T test, Spearman’s correlation and multiple logistic regression analysis. Results 131 serum tests for INF and 48 - for ADA were performed in 101 pts (mean age 50.2 and disease duration 9.9 years). Among responders 51 pts received INF and 16 pts – ADA. Among non-responders 34 pts had no response and 10 pts losed response ( 24 pts – INF; 20 pts - ADA). Levels (µg/ml, mean, SD) of INF and ADA in responders 4.2(2.3) and 7(5.95) were significantly higher than in non-responders1.09(0.45) and 2.9(0.45) respectively; levels of anti-INF-Ab and anti-ADA-Ab in responders 4.59(1.0) and 0.1(0) were significantly lower than in non-responders 13.13(6.1) and 8.1(1.0). Patients with RA and ankylosing spondylitis had significantly higher Ab levels than pts with psoriatic arthritis: 8.37(3.8), 9.6(0.3) and 3.5(0)µg/ml respectively. High anti-INF-Ab or anti-ADA-Ab levels predicted treatment discontinuation. In all non-responders with low INF/ADA levels and low anti-INF-Ab/anti-ADA-Ab the shortening of re-treatment intervals lead to significant improvement (Table 1). Conclusions Assessment of immunogenicity of anti-TNF monoclonal antibodies proved useful imformation for guiding the therapy in autoimmune diseases with suboptimal clinical response. Patients with low INF/ADA levels and low levels of corresponding Ab may benefit from increasing the drug dose or decreasing of re-treatment intervals. In pts with negligible serum levels of INF/ADA and high levels of corresponding Ab the therapy should be switched to a different drug. Disclosure of Interest: None Declared
    Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A442-A443. DOI:10.1136/annrheumdis-2013-eular.1334 · 10.38 Impact Factor