Kohava Toledano

Pulmonary Arteries Involvement in Takayasu's Arteritis: Two Cases and Literature Review

OBJECTIVES To review pulmonary arteritis (PA) complicated by pulmonary arterial hypertension (PAH) in Takayasus arteritis (TA). METHODS Two cases of PA and PAH in TA patients and similar cases published in the Medline database from 1975 to 2009 were reviewed. RESULTS Forty-six cases (females 89.1%, Asians 65%, mean age 34.6 years) were analyzed, 42.2% of which had PAH. Isolated PA was reported in 31.8%. Respiratory symptoms were presented as dyspnea (75.5%), chest pain (48.9%), hemoptysis (42.2%), and cough (17.7%). Hypertension, vascular bruits, and diminished/absent pulses were reported in 48.9% of patients. A diagnosis of PA was based on abnormal uptake on pulmonary perfusion scan and a finding of stenosis, narrowing, occlusion, and irregularity on computed tomography or magnetic resonance imaging, and/or pulmonary angiography. Patients were treated with glucocorticoids (77.5%), disease-modified antirheumatic drugs (35%), and warfarin (20%); only a few were treated with biological agents. Vascular procedures were performed in 52.5% of cases, on pulmonary arteries in 37.5% with good results. The outcome was death in 20.5% of PA patient and 33.3% in PAH patients. CONCLUSIONS TA may be complicated by life-threatening PA and PAH. Clinical signs are not specific and may be masked by involvement of the aorta and its branches. Treatment with glucocorticoids and disease-modified antirheumatic drugs has only partial effect, which may be intensified by biological agents. Invasive procedures on pulmonary arteries may be a complementary option. PA and PAH in TA patients should be recognized early and treated promptly for prevention of irreversible vascular damage.

Large leg ulcers due to autoimmune diseases

Summary Background Large leg ulcers (LLU) may complicate autoimmune diseases. They pose a therapeutic challenge and are often resistant to treatment. To report three cases of autoimmune diseases complicated with LLU. Case Report Case 1. A 55-year old woman presented with long-standing painful LLU due to mixed connective tissue disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV cyclophosphamide (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot debridement and autologous skin transplantation were performed and the LLU healed. Case 2. A 45-year old women with MCTD developed multiple LLU’s with non-specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ), azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3. A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful LLU’s due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100 mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and infliximab (5 mg/kg) were instituted and the LLU’s healed. Conclusions LLU are extremely resistant to therapy. Combined use of multiple medications and services are needed for healing of LLU due to autoimmune diseases.

Ultrasound investigation of the glenohumeral joint by anterior access in patients with rheumatoid arthritis and healthy controls.

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.

Early Repolarization: Innocent or Dangerous?

Abstract:Electrocardiographic (ECG) findings of wide QRS complexes in right precordial leads with saddle ST elevation in patients with polyarthritis, palpitations and family history of syncope urged us to review early repolarization syndrome (ERS). ERS is commonly seen in young men. The main ECG features are as follows: wide spread concave ST-segment elevation, more in the precordial leads (usually V2–V4); notching or irregular contour of J point and prominent concordant T waves with large amplitude. ERS was historically considered as a benign ECG variant. In recent years, it has emerged as a marker for increased risk of sudden cardiac death. The purpose of this review was to describe the ECG manifestations of this syndrome and to review the literature concerning its arrhythmogenic potential. The authors found it important not only discussing the rate of ERS life threatening but also to reemphasize its differences from other syndromes. Some of the last are much more dangerous: acute myocardial infarction and Brugada syndrome. The tables will be helpful for physicians to distinguish ERS from other syndromes in patients with chest pain and ST elevation.

THU0343 The effect of adalimumab on clinical manifestations and pro-inflammatory cytokines milieu in patients with behcet's disease

Background Behcets disease is a multisystemic chronic relapsing inflammatory disease, classified among the vasculitides. The aetiology of Behcets disease is unknown. Several cytokines, among them TNF-α, are involved in the pathogenesis of the disease. Objectives We aimed to assess efficacy and safety of Adalimumab (ADA) in patients with active Behcets arthritis not responding to one or more DMARDS and to assess the impact of treatment on the cytokine milieu. Methods Eligible patients (pts) with active arthritis were enrolled in a 24 weeks single center prospective open-label study. Pts who relapsed within 12 weeks following ADA discontinuation could enter a 3 year extension study. The efficacy was assessed by 68 tender and 66 swollen joint count, patient visual analogue scale (VAS) for pain, physician overall disease activity VAS, health assessment questionnaire (HAQ), Behçets Disease Current Activity Form (BDCAF), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). TNF-α,IL-1β, IL-6, INF-γ, IL-10 and IL-17a were evaluated at baseline, after 24 and 48 weeks of treatment, by ProcartaPlex Human High Sensitivity – Immunoassay kit. Trough ADA serum levels and anti-drug antibodies were measured at baseline, week 24 and 48. Results Ten pts (6 females),age (mean, standard deviation –SD) 45 (8.4) years, with a disease duration of 11.6 (10) years, were enrolled and treated with subcutaneous ADA 40mg every 2 weeks for 24 weeks. The results are described in Table1. A statistically significant improvement was observed in swollen joint count, physician VAS and BDCAF and in IL-6 levels, but not in tender joint count or HAQ. Resolution of oral and urogenital ulcers was achieved in all pts. Significant reduction of pain was reported by 40% of pts. No relapse of uveitis or other disease manifestations occurred during the study. The reduction in IL-6 levels correlated with the physician VAS and BDCAF but not with HAQ. No correlation was found between change in IL-10 level and VAS pain. The levels of INF-γ, IL-17A, TNF-α were undetectable in all pts. IL-1β was elevated in 1 patient only. ADA serum trough levels were in the therapeutic range in 7/10 pts. One patient developed high antidrug antibodies titer and ADA serum trough level of 0 with a concomitant increase in VAS pain and IL-6 concentration. Another patient with low ADA trough levels and no antibodies improved after providing ADA weekly. The disease relapsed in 9/10 pts, within 4–6 weeks following ADA interruption, 7 pts enrolled into the extension study. Baseline mean (SD) 24 weeks mean (SD) P Swollen joints 4.6 (4.2) 0.6 (0.4) 0.006 Tender joints 19 (18.7) 12.6 (10.9) Non significant (NS) Physician VAS 51.5 (18.5) 24.5 (16) 0.002 Patient pain VAS 72 (19) 56 (33) NS BDCAF 5.4 (1.6) 2.1 (1.4) 0.001 HAQ 1.76 (0.8) 1.6 (0.9) NS IL-6 pg/ml 10.06 (13.4) 2.02 (0.8) 0.042 Conclusions ADA treatment was well tolerated and achieved a significant improvement in arthritis and mucocutaneous manifestations and lowered IL-6 serum concentration in all study pts but only 40% reported significant pain reduction. A subset of pts with insufficient improvement in joint tenderness and generalized pain may require comprehensive pain management besides anti-inflammatory therapy. Acknowledgements ABBVIE donated the study medication and supported the lab work Disclosure of Interest None declared

AB0653 Gastric Antral Vascular Ectasia in Systemic Sclerosis Patients: Long-Term Prognosis and Treatment

Background Gastric antral vascular ectasia (GAVE) is characterized by a pathognomonic endoscopic pattern, mainly represented by red spots either organized in stripes radially departing from pylorus, defined as “watermelon stomach”, or arranged in a diffused-way, the so called “honeycomb stomach”. In our previous work we found a prevalence of GAVE in 35% of systemic sclerosis (SSc) patients that had an upper gastrointestinal (GI) endoscopy for evaluation of symptoms. The main complication of GAVE is symptomatic anemia due to GI bleeding requiring blood transfusion. As the pathogenesis is unknown, the aim of the therapy is to decrease GI bleeding. Endoscopic therapy (endotherapy) is the mainstay of treatment with surgery reserved for severe refractory cases. The data on the efficacy of endotherapy and treatment requirements of SSc patients with GAVE is very limited. Objectives The aim of our study is to assess the treatment requirements of SSc patients with GAVE and the efficacy of endotherapy in particular. Methods Retrospective analysis of a prospectively maintained database of SSc patients followed in a tertiary referral center for SSc. Our cohort is part of the EUSTAR cohort. Statistical analysis: descriptive, students T test, Mann-Whitney test. Results Fifty SSc patients were diagnosed with GAVE. Seventeen patients (34%) suffered of symptomatic anemia and were treated with argon plasma coagulation (APC) for a mean (SD) of 4.5 (4.3) sessions per patient. The mean (SD) hemoglobin was 9.4 (1.7) gr% in the group who required endotherapy compared to 11.5 (1.3) in the group which did not need any intervention. Four patients needed more than 6 sessions of treatment. Mean (SD) follow up was 4.1 (2.4) years. Nine patients required a total of 73 packed blood cells units and another 4 had intravenous iron replacement. Four patients died during the first 2 years after diagnosis, none of them due to bleeding complications. None of the patients that survived more than 2 years required further endotherapy or blood transfusions. No significant complications of APC occurred. Interestingly, all those who survived,had received immunotherapy with cyclophosphamide or mycophenolate mofetil due to multisystem involvement and disease activity. Conclusions Long term survivors among SSc patients with GAVE had an excellent response to APC and did not require blood transfusions or endotherapy after 2 years follow up. All the long term survivors received immunotherapy. This observation might hint to the pathogenesis of GAVE in SSc. Disclosure of Interest None declared

AB0944 Us Investigation of Gleno-Humeral Joint by Anterior Access

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. Table 1. Data of US GHJ measurement: posterior, inferior and anterior view, rotator interval (RI) Transducer position Controls Rt Controls Lt RA Rt RA Lt p (Rt; Lt) (mm) (mm) (mm) (mm) Posterior 1.4±0.5 1.3±0.4 4.5±3.8 4.3±2.9 <0.001; <0.001 Inferior 1.7±0.5 2.1±0.7 3.6±2.9 3.9±2.8 0.001; 0.002 RI width 10.4±2.3 9.7±3.0 10.7±2.5 10.0±3.3 0.66; 0.79 RI height 7.6±1.3 7.4+/1.2 6.9± 2.2 7.2±1.7 0.27; 0.69 Anterior LV 1.1±0.4 1.1±0.3 2.0±1.3 2.4±1.1 <0.001; <0.001 Anterior TV upper 1.3±0.4 1.3±0.4 2.5±1.5 2.6±1.2 <0.001; <0.001 Anterior TV middle 1.2±0.4 1.2±0.3 1.6±0.9 1.9±0.8 0.002; <0.001 Anterior TV lower 1.1±0.4 1.2±0.3 2.5±1.9 1.9±1.2 <0.001; 0.005 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 Van Holsbeeck MT, et al. Musculoskeletal ultrasound. Mosby, St. Luis. 1991. Koski JM. Scand J Rheumatol 1991;20:49-51. Ptasznik R. Sonography of the shoulder. 2001. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2010

FRI0509 Upper Gastrointestinal Bleeding is Associated with Significantly Higher Mortality in Systemic Sclerosis Patients

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

FRI0157 Rheumatologic Manifestations in Inflammatory Bowel Disease Patients Referred to the Rheumatology Service in A Tertiary Referral Center

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, Spearmans correlation and multiple logistic regression analysis. Results Seventy pts suffered of Crohns 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

Marble pneumoconiosis associated with mixed connective tissue disease

Caplans syndrome: combination of pneumoconiosis and lung nodes due to seropositive rheumatoid arthritis (RA) is well known entity. We present 45 years old marble worker with fever, cough, and exertion dyspnoe with multiple lung nodes, infiltrates and fibrosis by chest CT and Raynaud syndrome with vascular finger tip lesions. Our patient had 7 years history of mixed connective tissue disease. Skin vascular lesions rapidly regressed after nifedipine therapy and methylprednisolone pulses. Substantial response of the lung disease to steroid and antibiotic therapy was not observed. Due to further respiratory failure the patient was underwent lung transplantation. Histology from removed lung showed dust laden macrophages with weak polarization positivity, advanced silicotic nodules with focal calcifications surrounded by chronic inflammation and massive fibrosis. No acid fast bacteria were found. Above mentioned findings extend a field of Caplans syndrome. Different dusts and other rheumatic diseases, a part from RA, might be implicated.