Petr Bradna

NSAID-Induced Enteropathy in Rheumatoid Arthritis Patients with Chronic Occult Gastrointestinal Bleeding: A Prospective Capsule Endoscopy Study

Background. The purpose of study was to evaluate the diagnostic yield of capsule endoscopy for NSAID-induced enteropathy and clinical, laboratory, and endoscopic characteristics of disease in patients with rheumatoid arthritis. Methods. 37 rheumatoid arthritis patients (30 women; mean age 55) treated with NSAIDs (>1 month), presented with anaemia and/or positive faecal occult blood testing, entered the study and underwent capsule endoscopy (EndoCapsule; Olympus), laboratory tests, and filled in questionnaires. Results. The prevalence of NSAID-induced enteropathy diagnosed by capsule endoscopy was 68% (25/37), classified as mild (red spots or erosions) in 18 (49%), moderate (10–20 erosions) in 4 (11%), and severe enteropathy (>20 erosions or ulcers) in 3 (8%) patients. We did not find statistically significant relationship between the enteropathy and gender, age, haemoglobin, leukocytes, albumin and CRP, or dyspepsia. The difference between subgroups of NSAIDs according to the COX specificity was not statistically significant. Conclusions. Capsule endoscopy is a highly accurate noninvasive method for evaluation of NSAID-induced enteropathy. It was revealed in a substantial section of the patients with rheumatoid arthritis and occult gastrointestinal bleeding, mostly classified as mild damage. No simple clinical or laboratory markers of the presence or severity of NSAID-induced enteropathy were recognised. This trial is registered with DRKS00004940.

Disease Activity Composite Indices in Patients with Rheumatoid Arthritis and Concomitant Fibromyalgia

We read with great interest the article by Coury, et al 1 comparing patients with rheumatoid arthritis (RA) and concomitant fibromyalgia (RAF). The ambiguous results of this study showed that patients with RAF had significantly higher disease activity measured by the 28-joint Disease Activity Score (DAS-28)2, but significantly more severe joint destruction was revealed in patients with RA. We examined 120 of our patients (29 men, 91 women) with RA according to the American College of Rheumatology (ACR) criteria3 on the presence of concurrent fibromyalgia (FM). All … Address correspondence to Dr. Toms, E-mail: toms.jan{at}seznam.cz

Case 1-2012: ANCA associated glomerulonephritis in combination with IgG4-positive mediastinal mass in a patient with ankylosing spondylitis treated with TNF alpha inhibitors.

47 ‐year ‐old man with ankylosing spondylitis was admit‐ ted with fever of unknown origin. diagnosis of ankylosing spondylitis was made 14 years ago based on occurrence of inflammatory back pain, bilateral sacroileitis and HLA B27 positivity. the patient was treated with non ‐steroidal anti‐inflammatory drugs; treatment with TNF alpha inhibi‐ tor (adalimumab 40 mg s.c. every other week) had been started ten months before admission. four months ago the patient started to be subfebrile or febrile (38 °c, sometimes with chills), he suffered from night swelling, fatigue, weight loss (5 kg during the last month) with normal appetite and without changes of bowel movements. the treatment with adalimumab was stopped two months ago. Before admis‐ sion, several tests and imaging methods were performed, however, the origin of the fever remained unclear (normal chest X ‐ray, abdominal ultrasonography, scintigraphy of the skeleton, otorhinolaryngologic examination, antinuclear fac‐ tor and anti dsdna antibodies as well as quantiferon tB gold were negative). with persistent fever he was admitted to our department of Rheumatology. Laboratory markers of inflammation were elevated (eryth‐ rocyte sedimentation rate 101mm/hour, cRp 110 mg/l), blood count and differential leukocyte count were nor mal, urine examination showed significant microsco‐ pic erythrocyturia (++++) and increasing proteinuria (0.74 g/day...1.2 g/day...2.64 g/day), serum creatinine was ini tially normal, subsequently the values were increasing (83...113...146...189...212 μmol/l). Paraprotein was not detected either in blood or in urine. infectious aetiology was not found (blood cultures repeatedly negative, as well as other cultures, also Mycobacterium species pcR in serum and urine negative). However, a significant titre of PRO3 anca antibodies (136.8 U/ml) was detected. high resolution ct (hRct) of the lung excluded a pneu‐ mopathy, but displayed a mediastinal mass in posterior mediastinum (190 × 32 × 53 mm), located perivertebrally, saddle shaped, in contact with dorsal aortic wall. fluoro‐ dexyglucose pet/ct revealed hypermetabolism of this mediastinal mass (figs. 1–3); another similar mass was found in the aortic arch area (20 × 8 mm, fig. 4), and still another under the bifurcation of abdominal aorta (30 × 35 × 10 mm, fig. 5). a ct ‐guided biopsy of the mediastinal mass was performed, followed by a kidney biopsy.

Application of the DETECT algorithm for detection of risk of pulmonary arterial hypertension in systemic sclerosis: data from a Czech tertiary centre

OBJECTIVE The early, simple and reliable detection of pulmonary arterial hypertension (PAH) in SSc (DETECT) study described a new algorithm for early detection of PAH in patients with SSc. The aim of this retrospective, single-centre, cross-sectional study was to apply a modified DETECT calculator in patients with SSc in the East Bohemian region, Czech Republic, to assess the risk of PAH and to compare these results with PAH screening based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 2009 guidelines. METHODS Sixty patients were recruited with a diagnosis of SSc (according to ACR criteria), aged 27-78 years. A modified DETECT algorithm using the modified parameter of (1.4 × right ventricle diameter)(2) in place of right atrium area was applied to all patients. Right heart catheterization (RHC) was performed in all patients with an estimated (by echocardiography) increased systolic pulmonary artery pressure ≥50 mm Hg in accordance with the ESC/ERS guidelines; however, RHC was not performed in patients solely recommended for RHC using the modified DETECT algorithm. RESULTS Using the modified DETECT calculator, 24/58 (41.4%) patients were recommended for RHC, compared with 14/58 (24.1%) when applying the ESC/ERS 2009 guidelines. PAH was diagnosed in 7/58 (12.1%) patients. During follow-up, PAH was diagnosed in six patients. Of these, four were modified DETECT score-positive for 2 years and all for 1 year before PAH diagnosis. CONCLUSION The modified DETECT algorithm detects all patients with PAH diagnosed according to ECS/ERS 2009 guidelines and RHC. Data of the 2-year follow-up indicate a possible positive predictive role for the modified DETECT calculator.

THE VEGF AND BMP-2 LEVELS IN PATIENTS WITH ANKYLOSING SPONDYLITIS AND THE RELATIONSHIP TO TREATMENT WITH TUMOUR NECROSIS FACTOR ALPHA INHIBITORS

INTRODUCTION Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes. AIM The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors. METHODS Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method. RESULTS In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum levels of CRP (r = 0.56; p = 0.00001) and the BASDAI value (r = 0.33; p = 0.015). CONCLUSION Significantly lower VEGF levels were found in patients treated with TNFα inhibitors versus the untreated patients. These findings are in harmony with some hitherto published analyses and may give evidence of a favourable effect of TNFα inhibitors on radiographic progression. Neither influence on the BMP-2 level by treatment with TNFα inhibitors nor correlation with VEGF levels was demonstrated.

The plausible association of MTHFR and ADORA2A polymorphisms with nodules in rheumatoid arthritis patients treated with methotrexate.

Objective The treatment of rheumatoid arthritis (RA) patients with methotrexate (MTX) is linked to the development or progression of rheumatoid nodules. The aim of this study was to determine whether folate and adenosine pathways-related single nucleotide polymorphisms might be predictive of increased nodule formation in RA patients treated with oral MTX. Methods A total of 185 Caucasian RA patients were enrolled in this cross-sectional study, all of whom fulfilled the 1987 RA criteria of the American College of Rheumatology; each patient had a history of MTX treatment. Results A higher frequency of the MTHFR 1298AA genotype was found in 17 (70.8%) of 24 patients with general nodules [odds ratio (OR)=3.08, 95% confidence interval (CI): 1.20–7.69] and in 14 (73.7%) of 19 patients who developed nodules during MTX treatment (OR=3.55, 95% CI: 1.22–10.32). In contrast, a negative association with nodules during MTX treatment (OR=0.29, 95% CI: 0.08–1.10) was found for 19 (79.2%) patients with the TT genotype (rs2298383) in the adenosine A2a receptor gene (ADORA2A). However, the significance did not remain upon correction for multiple testing. The combination of MTHFR 1298AA along with ADORA2A rs2298383 CC or CT genotypes occurring in one-third of RA patients showed a higher frequency of general nodules 15/59 (25.4%) as well as developing nodules during MTX treatment 13/59 (22.0%) in comparison with the overall studied group: 24/185 (13.0%) and 19/185 (10.3%), respectively. Conclusion This exploratory study indicates for the first time a plausible association of adenosine and folate pathways single nucleotide polymorphisms in nodules’ etiopathogenesis.

Methotrexate impact on radiographic progression in biologic-treated rheumatoid arthritis under clinical remission: A case report on monozygotic Caucasian twins:

We describe Caucasian monozygotic twin brothers with rheumatoid arthritis (RA) and discuss influence of predictors to methotrexate (MTX) outcome treatment. Single nucleotide polymorphisms (SNPs) of the MTX metabolic pathways were genotyped. Twins have multiple mutations: a CC mutation of SNP 1298A>C in methylenetetrahydrofolate reductase (MTHFR) gene, CC mutations of three SNPs in the adenosine receptor gene ADORA2A (rs3761422_4217241T>C, rs2267076_4221164T>C, rs2236624_4226593T>C), and a heterozygous genotype in SNPs ATIC_rs2372536_347C>G, MTHFD1_rs2236225_1958G>A. These mutations are known to predict a worse outcome of MTX treatment. The twins had different lifestyles (alcohol drinking and smoking in Twin 1, regular coffee consumption in Twin 2), but a very similar clinical presentation of the outset of RA, radiographic scoring according to the Sharp/van der Heijde method with an almost identical antibodies presentation. The period of the patients before anti-TNFα treatment was characterized by unsuccessful per oral MTX pharmacotherapy in both cases (a low effect of MTX in Twin 1; an early discontinuation of MTX due to an adverse event in Twin 2). In both twins, the outcome of well-controlled anti-TNFα treatment (co-medication with MTX in Twin 1) for 10 years was expressed as low disease activity measured using composite index DAS28. It is interesting that Twin 2 had an unfavorable radiographic scoring after a 10-year follow-up than Twin 1 in spite of the comparable DAS28 in Twin 2 and smoking in Twin 1. In conclusion, co-medication of MTX with biologics may impact on RA radiographic progression despite predicted bad MTX outcome based on pharmacogenetic analysis.

AB0565 Diffuse Alveolar Hemorrhage, Diagnosis, Treatment and 3-Year Prognosis in A Group of 32 Cases of Tertiary Centre

Objectives Diffuse alveolar hemorrhage (DAH) is severe, life-threatening syndrome, affecting the patients with systemic vasculitis and other systemic connective tissue diseases. It can be often the first manifestation of systemic disease. Frequently DAH is the acute incident, which often leads to the rapidly emerging respiratory and/or renal failure with requirement of ventilatory support and with high mortality rate. Methods Diffuse alveolar hemorrhage was diagnosed on the basis of bronchoscopy and CT examination in patients with rapidly progressive respiratory insufficiency or newly emerged hemoptysis. Artificial ventilation was started in majority of cases.Therapeutically were used high doses of steroids i.v. (1000 mg 3–5 times in the iv infusion), Cyclophosphamide pulse, and plasmapheresis in some cases. Results The group of patients consisted of 32 cases; the average age of patients was 54 years (20–71) years. In half of patients was the episode of DAH the first manifestation of the disease. 16 patients were pro3 ANCA-positive, 7 patients MPO-ANCA positive, 6 patient had known systemic connective tissue disease 46.8% of patients survive 3 years from the acute episode of DAH, including two with repeated hemorrhage. 15 patients died during the acute phase of the disease, 3 more died during next 3 years, two of them on an opportunistic infection. Steroids were used for all patients, cyclophosphamide in 71, plasmapheresis in 56%, and i.v. immunoglobulins for 6.25 percent of patients. Patients who survive 3 years after the acute episode, had significantly lower necessity of artificial ventilation (40 vs. 93%) against the fatal cases, unfavorable prognostic sign was long term connective tissue disease. Residual lung impairment is present in 53% of the surviving patients; the signs of pulmonary arterial hypertension are present in 20% of the surviving group. Conclusions Diffuse alveolar hemorrhage is a sudden life-threatening event with a high mortality rate (46%) in the acute phase and during the first 3 years after the acute episode (20% of survivors). Up to half of patients the episode of DAH may be the first manifestation of the disease. Survival of patient depends on rapid diagnosis and the initiation of intensive immunosuppressive therapy. Respiratory failure is the major negative quoad vitam prognostic factor. Suspect the diffuse alveolar bleeding is necessary always in the case of a rapidly progressive respiratory failure. Acute bronchoscopy and x-ray examination give diagnosis of DAH, which further specify the acute examination of ANCA antibodies (71% of the report was ANCA antibodies positive. Disclosure of Interest None declared

AB0166 The Levels of Soluble CD163 in Patients with Ankylosing Spondylitis

Background Innate immune cells play an important role in pathogenesis of spondylarthropathies (SpA) since the increased infiltration of macrophages, especially CD163+, has been proven in synovitis tissue in these patients. Objectives To evaluate the levels of soluble CD163 (sCD163) in patients with ankylosing spondylitis in comparison with patients treated for degenerative spinal disease. Methods Levels of sCD163 were measured by enzyme-linked immunosorbent assay in patients with established ankylosing spondylitis according to modified New York criteria (n=55) and were compared with control group - patients treated for degeneratve spinal disease (n=20). Furthermore, we compared the levels of sCD163 in patients with ankylosing spondylitis treated (n=21) and not treated (n=34) with tumor necrosis factor alpha inhibitors. Results The levels of soluble CD163 were significantly increased in group of patients with ankylosing spondylitis as compared with the control group (mean ± SEM 1670,8±91,6 ng/ml vs. 1131,5±80,3 ng/ml, p=0,0013). No significant difference was found between levels of soluble CD163 in patients treated and not treated with tumor necrosis factor alpha inhibitors (mean ± SEM 1805,2±184,8 ng/ml vs. 1587,8±94,4 ng/ml respectively, p=0,52). Conclusions Our finding shows, that CD163+ cells may play role in pathogenesis of spondylarthorpathies, particularly ankylosing spondylitis, and soluble CD163 may be applicable biomarker in this disorder. Acknowledgements Supported by MH CZ –DRO (UHHK, 00179906) Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4464

THU0315 Increasing Proportion of Concomitant Fibromyalgia in Rheumatoid Arthritis Cohort Corresponds to Growing Arthritis Activity Assessed by Composite Indices

Background Fibromyalgia (FM) is well described as a concomitant syndrome that can frequently accompany connective tissue diseases, especially rheumatoid arthritis (RA). In this epoch of modern biologic therapy and RA tight control effort it is essential to count various factors that can impact RA activity or modulate activity assessment. Objectives To compare proportional representation of FM in RA patients cohort according to increasing arthritis activity assessed by composite indices in a regional, monocentric, cross-sectional study. Methods Examination of 120 consecutive patients (pts) with RA was performed in the terciary outpatient rheumatology department. Diagnosis of concomitant FM was established according to ACR criteria (1990). Standard Manual Tender Point Survey was used for the examination of FM tender points. The following data were recorded: demographic data, tender point count (TPC), Fibromyalgia Impact Questionnarie (FIQ) score and RA activity composite indices (DAS-28, CDAI, SDAI). Short Form 36 items (SF-36) and Health Assessment Questionnaire (HAQ) were used for evaluation of quality of life (QOL) and functional disability, respectively. Statistical analysis was based on Students t-test or Fisher exact test (statistical significance level 0.05). Results Concomitant FM was diagnosed in 25 (20.8%) pts with RA, 4 men and 21 women. Comparing RA without FM (RAF-) and with FM (RAF+), there were no significant differencies in sociodemographic characteristics, laboratory inflammatory markers, RF and ACPA seropositivity. RAF+ pts in comparison to RAF- pts reached significantly higher scores of RA activity (DAS-28 5.35±1.1 vs. 3.67±1.4, p<0.0001) and disability level (HAQ 1.83±0.64 vs. 0.87±0.76, p<0.0001). Analysing RA subgroups on the basis of rising disease activity we found increasing proportion of RAF+ pts in the subgroup with higher activity (DAS-28 <3.1 – 2.7% RAF+ pts; DAS-28 3.2-5.1 – 13.5%; DAS-28 >5.1 – 54.8%, p<0.0001). Similar results were found using other composite indices CDAI and SDAI. Conclusions Concomitant fibromyalgia appears frequently in RA pts and has significant impact on the disease activity assessment and disability level because of altered pain perception. Patients with high disease activity measured by widely used composite indices are usually indicated for more intensive immunosuppressive or biologic therapy. But in this case it is necessary to realize this group contains higher portion of FM pts resulting in risk of wrong therapy reinforcement. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5942