J.M. de Llobet

SAT0351 Differences among patients with interstitial lung disease according to their systemic sclerosis subclassification

Background Systemic Sclerosis (SSc) has been widely studied from a purely global standpoint, but only a few trials have analysed patients with interstitial lung disease (SSc-ILD) as well. Objectives 1. Describe the clinical features of a cohort of patients with SSc and SSc-ILD. 2. Determine whether there are disparities among different types of SSc-ILD and their progression in patients with either limited (lcSSc) or diffuse involvement (dcSSc). 3. Ascertain whether there are disparities among different types of SSc-ILD and their progression according to the SSc-specific autoantibody (AAb). Methods Retrospective study of a cohort of patients with ILD-SSc controlled during an SSc consultation. The following variables were collected: sex, age, SSc and ILD progress in years, type of SSc and ILD, smoking, digital ulcers (DU), pulmonary hypertension, digestive disorders, cancer, SSc treatment, corticosteroid doses and lastly, lung function tests upon diagnosis, at treatment onset, and 24 months later. Additionally, a record was kept on the types of AAb present in every SSc. Qualitative and quantitative variables were compared in relation to the clinical and immunological sub-classification. Chi-square and Students T Tests were performed. A p-value≤0.05 was considered significant. Results out of 266 patients with SSc, data from 47 patients with ILD-SSc were gathered; 89.4% were female, with an age range of 66.09±15.1 years old, and 9.85±10.2 and 4.38±9.24 years of progression of their SSc and ILD respectively. 33 out of 47 sustained lcSSc, and both Scl-70/ATA (29.8%) and ACA (26.1%) were the most frequently found AAb. Non-specific interstitial pneumonia (NSIP) was the most common ILD radiological pattern (76.6%). Most patients with SSc underwent treatment (51.1%), 24% with mycophenolate mofetil (MMF); 36.2% of the patients had been concomitantly administrated corticosteroids with a mean prednisone dose of 15.73±10.3 mg/d. Upon comparing patients with lcSSc and dcSSc, prevalence of DU was higher in those with dcSSc (p<0.01), MMF was less frequently used (p<0.02), rituximab was more usually employed (p<0.03), and they presented worse values of FEV1/FVC ratio after 24 months of treatment (p<0.03). No differences were observed as to either type of ILD or progression. However, when variables were analysed regarding AAb in SSc, patients with ACA presented both fewer DU (p<0.02) and NSIP pattern (p<0.02), and more frequent compromise of the small airway (p<0.01), they were younger and thus, they had had shorter progression of the disease. ILD diagnosis was made significantly earlier in those patients with RNA polymerase, and later in those with anti-U1RNP. No AAb was observed associated with neoplasia. Considering the types of ILD, patients with NSIP pattern were younger (p0.054) and presented worse spirometric values. Conclusions In terms of ILD-SSc patient stratification, sub-classification by AAb appears to be more specific than the clinical sub-classification. ACA is related to less frequency of NSIP pattern. Unlike what has been described for SSc from a global point of view, in patients with ILD-SSc no association between AAb and neoplasia could be established. Disclosure of Interest None declared

AB0717 Conduction disturbances in a group of patients with axial spondyloarthropathy

Background Cardiac conductance disturbances are known to be one of the many extra-articular manifestations of Ankylosing Spondilitis but not as well related to axial spondyloarthropathies. Objectives Description of conduction disturbances found in a group of patients with Axial Spondyloarthropathy (AxSpa) that met ASAS criteria. Methods Clinical and demographic variables of 78 patients with AxSpa were registered. It included cardiovascular risk factors as well as cardiacvascular adverse events. All of them had a routine electrocardiogram done which were analized by a cardiologist. Results 48 of the 78 patients were men, with a mean age of 61 with standard deviation (SD) of 14. The mean time of evolution of the disease was 23 years (SD ±16). HLA-B27 was prevalent in 54 (69.2%). The sacroileitis was found in radiologic examination of 72 (92.2%), and 6 (7.7%) of them presented edema in magnetic resonance imaging. Other clinical traits were: 43 (55.1%) peripheric arthritis 43, 8 (10.3%) dactilitis, 33 (42.3%) enthesitis, 16 uveitis (20.5%), 2 (2.6%) inflammatory bowel disease and psoriasis 34 (43.3%). The following cardiovascular risk factors were registered: 25 (32%) smokers, 42 (53%) hypertension, 32 (41%) dislipemia, 9 (12%) diabetes, 9 (12%) hyperuricemia and 20 (20%) obesity. 14 patients had structural cardiopathy (11 ischemic cardiopathy and 3 aortic valvulopathy). The electrocardiographic register showed conductance disorders in 20 patients (25.6%). The details of these findings are specified in table 1. First grade auriculoventricular block 5 Second and third grade auriculoventricular block 2 Left anterior fascicular block 1 Right bundle branch block 2 Unspecific intraventricular conduction disorder 4 Bachmann interatrial conduction disorder 1 Conclusions A quarter of our series of presented conduction disturbances in electrocardiography. The relation with disease evolution, as in Ankylosing Spondilitis remains yet to be analized. Disclosure of Interest None declared

AB0826 Hyperuricemic patients with systemic sclerosis do not present higher incidence of pulmonary hypertension but have worse echocardiographic parameters

Background Uric acid (UA) serum levels are increased in conditions that affect the oxidative metabolism. Several studies have demonstrated increased UA levels in patients with pulmonary hypertension (PH) and its relation to prognosis. There are few studies demonstrating the clinical significance of hyperuricemic in patients with PH secondary to systemic sclerosis (SSc). Objectives To determine whether patients with SSc and PH have a higher frequency of hyperuricemica and to determine if there is greater frequency of PH in hyperuricemic and SSc patients. Methods Retrospective review of cohort of patients with SSc from rheumatology unit of a tertiary university hospital. Hyperuricemia was considered if UA levels were higher than 6,8 mg/dl and PH in either the presence of echocardiographic signs of PH or pulmonary artery pressure (PAP) >40mmHg. The following variables were collected: sex, age at diagnosis, type of SSc (limited, diffuse, earlySSc or without skin involvement), presence or absence of: digital ulcers (DU), sclerodermic renal crisis (SRC), interstitial lung disease (ILD), use of hyporuricemic therapy, colchicine and NSAIDs. Uric acid levels, renal and respiratory function parameters and echocardiographic parameters were recorded. To compare groups of qualitative variables chi-square or Fisher test were used, and T-test for quantitative variables. Statistical significance level was set to p values ≤0.05. Results A total of 136 patients with SSc (93,4% female, age at diagnosis 51,02±15,51 years) were included. Ninety five out of 136 presented limited SSc, 21 diffuse SSc, 19 early SSc and 1 sine scleroderma. One third (31,6%) of the patients presented DU along their disease, 28,7% ILD, 21,3% PH and 2,2% SRC. Patients with PH presented ILD more frequently (50% vs 23,36% p =0.006), but the frequency of DU and SRC were not increased. Parameters of DLCO (Diffusing capacity for carbon monoxide)and FVC (Forced vital capacity) were significantly lower in patients with PH (56,7±19,1% vs 80,13 vs 19,13% and 77,86±23,42 vs. 95,09±18,3 p <0,01). Higher ratio FVC/DLCO and thicker than the IVT (11,52±3,16 vs 10,02±2,18 p =0.03) were observed in these patients. No differences in the levels of UA in both groups were detected. Patients with hyperuricemia did not have higher frequency of PH (35,7 vs 21,5%, p ns) than those without, but they did show a higher frequency of SRC (p <0.05). When comparing different echocardiographic parameters, patients with hyperuricemia had higher values of estimated PAP (45,5±8,081 vs 33,41±9,87 mmHg, p =0,024), lower TAPSE (1,6±0,14 vs 2,52±1,78 cm, p =0,01) and increased IVT thickness (12,44±2,78 vs 10,25±2,3 mm, p<0.05). Conclusions Patients with PH had a higher ILD frequency. There was no difference in the frequency of hyperuricemia between groups. Hyperuricemic patients did not show a higher PH frequency, nevertheless they showed worse echocardiographic parameters. The presence hyperuricemia was also associated with higher frequency of SRC. Furthers works are needed to evaluate the effects of UA in SSc. Disclosure of Interest None Declared

AB0806 Rituximab in clinical practice for the treatment of interstitial lung disease refractory to cyclophosphamide in patients with diffuse systemic sclerosis

Background Systemic sclerosis or scleroderma (SSc) is a connective tissue disease which frequently presents lung affectation, being the principal cause of death in these patients. Currently, only cyclophosphamide (CyC) has shown efficiency to treat this complication. However, this efficiency is modest and not kept through the time. Several medicines have been tested for the treatment of this complication with controversial results. Rituximab (RTX) seems to show improvement in patients with SSc and Interstitial Lung Disease (ILD) refractory to others treatments, but there are not pivotal assays in this regard and the experience is limited. Objectives To study the evolution of Pulmonary Function Test (PFT) in patients with SSc affected by ILD refractory to usual treatment and have made at least one cycle of Rituximab. Methods Multicenter observational prospective study in patients with ILD-SSc was performed. These patients had one cycle of two Rituximab infusions for ILD and previously had realized CyC, azathioprine or mycophenolic acid with treatment failure. We evaluated the following data: gender, age, onset age of Raynaud’s phenomenon, age at diagnosis of SSc, age at diagnosis of ILD, ILD type, total dose of CYC, use of concomitants steroids, and other immunosuppressive agents. PFT outcome after each therapy and after 4 months of treatment with RTX was included. Results We collected the data of four patients who realized one complete cycle of treatment with RTX. Patients were women and presented diffuse cutaneous shape with antitopoisomerase I antibodies. The radiologic affectation was Non-Specific Interstitial Pneumonia (NSIP) in all cases. Patient’s characteristics are showed in table 1. The patient who presented the best response to RTX (Patient 4) had the highest dose of CyC accumulated previously. As a whole, patients presented a worsening of the predicted value of FVC and DLCO after treatment with CyC. Four months later of RTX infusion, we did not observe any worsening in the values of FVC beside of a trend to improve the values of DLCO. The best response in concern to respiratory function parameters was not related with taking concomitant or accumulated dose of other drugs different to CYC. Age Age at diagnosis Age at ILD diagnosis FVC at ILD diagnosis (%) DLCO at ILD diagnosis (%) FVC post CyC (%) DLCO post CyC (%) FVC post RTX (%) DLCO post RTX (%) Cumulative CyC dose (g) Patient 1 51 31 39 53 80 40 28.9 51.4 31.4 21 Patient 2 35 28 28 47.8 38 38.6 16 37.5 15.7 20 Patient 3 65 58 58 49.8 40.8 37.9 30.7 15 Patient 4 52 47 47 62 55 56 45 60 61 27 Mean ± SD 50.75±12.28 39±13.49 43±12.65 53.15±6.28 53.45±19.2 44.87±9.67 29.97±14.53 44.9±13.25 36.03±23 20.43±5.23 Conclusions Rituximab could be an alternative to the treatment and stabilization for interstitial lung disease in patients with SSc, however experience remains limited. Disclosure of Interest None Declared

AB0189 Polymorphisms in genes involved in the metotrexate action mechanism. are they associated with response/toxicity of the drug?

Background Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease of unknown etiology. Methotrexate (MTX) is the first-line treatment option for newly diagnosed RA patients. However, only 50–70% of the patients will respond to MTX therapy and up to one third will discontinue treatment because of toxicity. Objectives Studying SNPs (single nucleotide polymorphisms) described in the literature for its possible role as biomarkers of response and / or toxicity to MTX, in Spanish patients diagnosed with rheumatoid arthritis. Methods We analyzed 27 TagSNPs in 5 candidate genes (DHFR, TYMS, MTHFR, ATIC and CCND1) involved in the action mechanism of MTX. We studied its association with the therapy-related efficacy and toxicity. One hundred and twenty-four adult patients with RA treated with MTX monotherapy were studied. TagSNPs within these genes were selected using bioinformatic tools and were genotyped using a 48.48 dynamic array on the BioMark system. Toxicity was measured as the time interval that MTX was administered. Efficacy was assessed using the DAS-28 EULAR response criteria. Results Clinical data of the patients are shown in Table 1. The univariate analyses showed significant association with toxicity in the dominant model with two TagSNPs in the ATIC gene: rs10197559 (P=0.05) and rs16853826 (P=0.04). Two TagSNPs in the MTHFR gene showed significant association with response in the dominant model: rs11121832 (P=0.02) and rs17421511 (P=0.02). Conclusions Polymorphisms in the ATIC and MTHFR genes may be considered as putative pharmacogenetic markers in RA patients treated with MTX on monotherapy. References Kinder AJ, Hassell AB, Brand J, Brownfield A, Grove M, Shadforth MF. The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology 2005;44:61–6 Wessels JA, van der Kooij SM, le Cessie S, Kievit W, Barerra P, Allaart CF, et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoidarthritis. Pharmacogenetics Collaborative Research Group. Arthritis Rheum 2007; 56: 1765–75 Acknowledgements Societat Catalana de Reumatologia. Disclosure of Interest None Declared

AB0805 Nailfold capillaroscopy findings are different between patients with U1RNP antibody and systemic sclerosis or patients with systemic lupus erythematosus and U1RNP antibody

Background Nailfold capillaroscopy (NC) is the best tool to study microcirculation in patients with Raynaud’s phenomenon (RF) or patients with connective tissue diseases. There are some characteristic capillaroscopy findings in systemic sclerosis (SSc) patients, like presence of giant capillaries (GC) or loss of capillary density (LCD). Patients with Systemic Lupus Erythematosus (SLE) and RF may present nonspecific changes in the NC, but sometimes NC in SLE patient can simulate SSc findings. Anti-U1RNP antibodies may be present in both entities and are associated with a greater number of alterations in NC. Objectives To Determine the existence of differences between the findings of nailfold capillaroscopy in patients with SSc or SLE that present U1RNP antibodies. Methods Patients with SSc o earlySSc (eSSc) and positive determination of anti-U1RNP antibodies were included. Afterwards these patients were compared with a cohort of patients with SLE with anti-U1RNP antibodies. In both groups we studied in NC the following findings: presence o absence of giant capillaries (GC), angiogenesis and loss of capillary density (LCD). We compare findings with Chi-Square or Fisher’s test when it was needed. Statistcial analysis were performed by SPSS program v17.0 Results One hundred thirty-five SSc patients (93.4% women) and 76 SLE patients (94.7% women) were included. Determinatio of anti U1RNP abs were performed in 134 SSc patients and in 67 SLE patients. SLE patients had more U1RNP antibodies (10/134 [7.4%]) than SSc patients (13/67 [19.4%];p=0.012). NC showed GC, loss of capillary density and angiogenesis in 71.4%, 100% and 100% in SSc patients with U1RNP antibodies. SLE patients presented less pathological findings in NC that SSc patients (GC in 38.4%, LCD in 46.1% and angiogenesis in 69% of patients). A significant difference in NC between SSc and SLE patients were found in capillary density (lower in patients with SSc (p=0.04). Conclusions AntiU1RNP antibody is find more frequently in SLE patients than in SSc patients. Patients with SSc and U1RNP have more loss of capillary density in NC than SLE patients. Presence or absence of Loss of capillary density in patients with undifferenciated connective tissue disease with anti-U1RNP, or patients classified as mixed connective tissue disease could be useful to predict witch patients will develop SSc or SLE. We need more studies to determinate the use of NC in patients with antiU1RNP antibodies. Disclosure of Interest None Declared

SAT0435 Profile and degree of hyperglycemia after the infiltration of intrarticular corticosteroids to patients with and without type 2 diabetes mellitus

Background Corticosteroids (CS) are widely used in medicine for the treatment of multiple processes. In rheumatology, infiltrations with corticosteroids are indicated to relieve pain and improve joint limitation. Adverse effects of corticosteroids such as hyperglycemia are well known; nevertheless the existing information about the effects of the intrarticular administration is very scanty. Objectives The aim of this study was to define the profile and degree of hyperglycemia after intrarticular administration of triamcinolone acetonide to patients with and without type 2 diabetes. Methods It was an observational study. Twenty-one patients were included (9 with and 12 without type 2 diabetes). All of them received an intrarticular infiltration of 40 mg of triamcinolone acetonide and 1 ml of mepivacaine in a knee or a shoulder. All patients received a glucometer in order to determinate the glycemias before and 2 hours after breakfast, lunch and dinner, the previous day and during the 6 days after the procedure. A descriptive analysis, including demographic and clinical data, and a comparative analysis of mean glycemic data were performed. The results were analyzed using the SPSS’s v19.0 statistical package. Results Patients without diabetes showed an increase of glycemic index 48 hours following the infiltration, whereas it wasn’t observed in the diabetic patients. Likewise, we observed a statistically significant increase of the postprandial glycemia (167,36±58,39 vs 174,25±69,42mg/dl; p=0,025) of the day of the infiltration and in the determinations before breakfast (111,40±23,71 vs 135,77±62,26 mg/dl; p=0,008) and post lunch (152,089±25,9 vs 181±60,63 mg/dl; p=0,002) of the following day. Conclusions Type 2 diabetic patients do NOT need an increase of antidiabetic treatment after the intrarticular administration of 40 mg of acetone triamcinolone, provided that they do not present glycemic alterations after 6 days of the infiltration. On the other hand, the non-diabetic patients, present an hyperglycemic moderate and autolimited effect, without clinical significance. References Habib GS, Abu-Ahmad R. Lack of effect of corticosteroid injection at the shoulder joint on blood glucose levels in diabetic patients. Clin Rheumatol.2007;26:566–8. Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med. 1994;236:619–32. Blackburn D, Hux J, Mamdani M. Quantification of the risk of corticosteroid induced diabetes mellitus among the elderly. J Gen Intern Med. 2002;17:717–20. Disclosure of Interest None Declared