F. Barcelos

Association study of IL10 and IL23R-IL12RB2 in Iranian patients with Behçet's disease.

OBJECTIVE Independent replication of the findings from genome-wide association studies (GWAS) remains the gold standard for results validation. Our aim was to test the association of Behçets disease (BD) with the interleukin-10 gene (IL10) and the IL-23 receptor-IL-12 receptor β2 (IL23R-IL12RB2) locus, each of which has been previously identified as a risk factor for BD in 2 different GWAS. METHODS Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and 42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD controls. Population stratification was assessed using a panel of 86 ancestry-informative markers. RESULTS Subtle evidence of population stratification was found in our data set. In IL10, rs1518111 was nominally associated with BD before and after adjustment for population stratification (odds ratio [OR] for T allele 1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [P(unadj) ] = 2.53 × 10(-2) ; adjusted P [P(adj) ] = 1.43 × 10(-2) ), and rs1554286 demonstrated a trend toward association (P(unadj) = 6.14 × 10(-2) ; P(adj) = 3.21 × 10(-2) ). Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni correction for multiple testing, the most significant of which were rs17375018 (OR for G allele 1.51, 95% CI 1.27-1.78, P(unadj) = 1.93 × 10(-6) ), rs7517847 (OR for T allele 1.48, 95% CI 1.26-1.74, P(unadj) = 1.23 × 10(-6) ), and rs924080 (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 × 10(-5) ). SNPs rs10489629, rs1343151, and rs1495965 were also significantly associated with BD in all tests performed. Results of meta-analyses of our data combined with data from other populations further confirmed the role of rs1518111, rs17375018, rs7517847, and rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R-IL12RB2 were detected. Results of imputation analysis highlighted the importance of IL23R regulatory regions in the susceptibility to BD. CONCLUSION These findings independently confirm, extend, and refine the association of BD with IL10 and IL23R-IL12RB2. These associations warrant further validation and investigation in patients with BD, as they may have implications for the development of novel therapies (e.g., immunosuppressive therapy targeted at IL-23p19).

Effects of gustatory stimulants of salivary secretion on salivary pH and flow in patients with Sjögren's syndrome: a randomized controlled trial.

OBJECTIVES To compare salivary pH changes and stimulation efficacy of two different gustatory stimulants of salivary secretion (GSSS) in patients with primary Sjögren syndrome. SETTING Portuguese Institute for Rheumatological Diseases. DESIGN Double-blind randomized controlled trial. SUBJECTS Eighty patients were randomized to two intervention groups. Sample size was calculated using an alpha error of 0.05 and a beta of 0.20. MATERIALS AND METHODS Participants were randomly assigned to receive a new GSSS containing a weaker malic acid, fluoride and xylitol or a traditionally citric acid-based one. Saliva collection was obtained by established methods at different times. The salivary pH of the samples was determined with a pH meter and a microelectrode. MAIN OUTCOME MEASURES Salivary pH variations and counts of subjects with pH below 4.5 for over 1 min and stimulated salivary flow were the main outcome measures. RESULTS Both GSSS significantly stimulated salivary output without significant differences between the two groups. The new gustatory stimulant of salivary secretion presented an absolute risk reduction of 52.78% [33.42-72.13 (95% CI)] when compared with the traditional one. CONCLUSIONS In Xerostomic Primary Sjögren syndrome patients, gustatory stimulants of salivary secretion based on acid mail only with fluoride and xylitol present similar salivary stimulation capacity when compared to citric acid-based ones, besides significantly reducing the number of salivary pH drops below 4.5. This could be related to a diminished risk for dental erosion and should be confirmed with further studies.

Crosstalk between inflammation, iron metabolism and endothelial function in Behçet’s disease

Behçets disease (BD) is a rare chronic vasculitis of unclear etiology. It has been suggested that inflammatory response has an important role in BD pathophysiology. Herein, we aimed to study the interplay between inflammation, iron metabolism and endothelial function in BD and search for its putative association with disease activity. Twenty five patients clinically diagnosed with BD were selected and twenty four healthy age-sex matched individuals participated as controls. Results showed an increase of total number of circulating white blood cells and neutrophils, serum transferrin, total iron binding capacity, mieloperoxidase (MPO), ceruloplasmin (Cp), C reactive protein, β2 microglobulin and Cp surface expression in peripheral blood monocytes in BD patients comparatively to healthy individuals (p < 0,05). Of notice, the alterations observed were associated to disease activity status. No significant differences between the two groups were found in serum nitric oxide concentration. The results obtained suggest an important contribution from innate immunity in the pathogenesis of this disease. In particular, surface expression of leukocyte-derived Cp may constitute a new and relevant biomarker to understand BD etiology.

AB1168 Touch study: technology and outcomes used in clinic in a day hospital

Background Patient reported outcomes PRO are a key element in the global evaluation of patients, especially those followed in a day hospital. The use of touchscreen computers is one of the new features in the day hospital of Instituto Português de Reumatologia. Objectives to evaluate the transition from paper to touchscreen computers technology of the PRO in use in Reuma.pt Methods We considered a step up model of comparison with 2 months intervals one before the use of the touchscreen computers, one two months after the introduction of touchscreen computers and a third after an intermediate evaluation (comparison between interval 0 and 1) of the results.A specific formation to physicians and nurses to be aware of missing data from non-total completion of the questionnaires was introduced between the first and second evaluation. The percentage of questionnaires totally completed by number of patients were obtained for every period and diagnosis Results 631 day hospital appointments were evaluated according to diagnosis and interval and the percentage was obtained (Table 1)Table 1. Results comparing questionnaires by diagnosis and intervals Paper interval 0 Interval 1 Interval 2 (Sept –Nov 15) (Nov 15- Jan 16) (Jan – Mar 16) AS N N Quest. Pct. N N Quest. Pct. N N Quest. Pct. BASDAI 95 95 100,00% 92 87 94,57% 93 92 98,92% BASFI 95 94 98,95% 92 89 96,74% 93 92 98,92% EQ5D 95 91 95,79% 92 85 92,39% 93 88 94,62% AsQol 95 88 92,63% 92 83 90,22% 93 85 91,40% SF-36 95 80 84,21% 92 72 78,26% 93 77 82,80% HADS 95 27 28,42% 92 87 94,57% 93 91 97,85% FACIT 95 93 97,89% 92 91 98,91% 93 92 98,92% RA HAQ 112 111 99,11% 124 124 100,00% 115 114 99,13% SF-36 112 96 85,71% 124 101 81,45% 115 98 85,22% HADS 112 9 8,04% 124 111 89,52% 115 114 99,13% FACIT 112 108 96,43% 124 122 98,39% 115 114 99,13% EQ5D 112 105 93,75% 124 119 95,97% 115 113 98,26% Only HADS had a significative (p<0.000) improvement for every disease, with the use of the touchscreen computers from interval 1 to 2. On our intermediate evaluation comparing paper to tablet we saw a lower percentage of questionnaires fully completed (although not statistical significative) and a formal awareness formation addressing the causes was made with all the physicians and nurses of the day hospital. The PRO from Reuma.pt was not developed for tablets and some issues regarding missing data associated with that was found Conclusions The use of technology can contribute for better data in Reuma.pt and other national registries by saving time (medical and nurse) for clinical evaluation, by integrating patients in their evaluations and by cost reduction, and carbon footprint. Issues regarding the adaptability of software to tablet technology have to be addressed to insure an overall improvement. Disclosure of Interest None declared

AB0013 Is there immune disregulation in non-sjÖgren sicca syndrome? a study of blood lymphocyte subpopulations

Background A large number of patients with sicca syndrome not fulfilling Sjögrens syndrome (SS) classification criteria, present manifestations of autoimmunity, like arthritis, Raynauds, rash or hematologic disturbances, and have anti-nuclear antibodies, lacking however more specific antibodies. The designation Undifferentiated Connective Tissue Disease was coined to refer to those patients, and some will eventually progress to a definite disease, of which SS would be a likely candidate. Immune cell disturbances could be progression markerr, since diseases like pSS have distinct lymphocyte profiles. Objectives We aim to study the circulating lymphocyte subsets in non-Sjögren sicca patients (n-SS), and compare them with pSS and healthy controls. Methods We included 65 n-SS patients, 53 pSS patients (2002 AECG criteria) and 22 healthy controls. Lymphocyte subsets were characterized by flow cytometry, including follicular and regulatory T cells and naïve, mature, memory, plasmablasts and regulatory B cells. Statistical analysis was performed with GraphPad, and significance was considered for p<0.05 Results Comparing to controls, n-SS patients had lower counts of T cells (p=0.016), with lower CD4 (p=0.0028), however that difference was not as pronounced as between SS and controls. n-SS patients had higher percentages of CD4 (p=0.0005) and lower CD8 percentages (p=0.0009) than pSS. Additionally, there was a decrease in absolute counts of Tregs (p=0.0028) in n-SS patients compared to controls, which was less pronounced than the comparison between SS and controls (p=0.0008). Th17 cells were decreased in SS compared to controls (p=0.0005), but not in-SS patients. Compared with controls, both n-SS and SS patients presented decreased absolute count (p=0.0001 and p<0,0001, respectively) of CXCR5+ Tfh cells, with no differences between n-SS and SS patients. However, higher levels of IL21+CD4 T cells and Tfh1 cells were found comparing SS patients with both controls (p=0,0209 and p=0,0092 respectively) and n-SS patients (p=0,0051 and 0,0028 respectively). Absolute counts of memory, unswitched and switched memory cells in n-SS patients present intermediate levels between controls with significantly higher levels, and SS patients with significantly lower levels. Accordingly, using the Bm1–5 classification, we have found decreased Bm1 (p=0.004), eBm5 (Abs, p=0.0273) and Bm5 cells (Abs, p=0.0444) in n-SS patients compared to controls. Though not significant, there was an increase in eBm5 (Abs, p=0.063) and Bm5 cells (Abs, p=0.05) in n-SS compared to SS patients. Again, CD24+CD27+ Bregs were also decreased in n-SS patients compared to controls (p=0.036), but increased in n-SS compared to SS patients (p=0,0007). Conclusions Our data showed that n-SS patients present immune disregulation, represented by alterations in the B cell compartment but also in Tfh subset, known to modulate the humoral immune response. Although less pronounced, these modifications resemble the ones found in SS patients. Wether n-SS is a stage in the evolution to SS remains to be clarified. The identification of a characteristic disregulation of the immune system in n-SS could be usefull for diagnostic and prognostic purposes. Disclosure of Interest None declared

THU0536 Remission and Re-Treatment of Patients with Paget's Disease of Bone Treated with Zolendronic Acid – A Single Center 10 Year Experience

Background Treatment of Pagets Disease of Bone (PDB) has been revolutionized by the use of zolendronic acid (ZA). Patients usually have a dramatic response to treatment with normalization serum alkaline phosphataise (ALP) levels and a longer period of clinical remission, compared with other class agents. Data from long-term use are scarse. Objectives Evaluate the effectiveness and safety of ZA in PDB patients, as well as remission, re-treatment rates and side effects in our outpatient population since 2005. Methods A retrospective study of PDB patients treated with 5 mg ZA intravenous infusion at our day-care center. Follow up time, demographic and clinical characteristics, previous therapeutic agents, rate of response, number and reasons of re-treatment(s) and rates of adverse events were collected. A descriptive statistic analysis was made. Results 48 patients, 60% female, mean age of 75 years, with a median time since the diagnosis of 12.3 years. The disease was poliostotic in 73% of the patients and pelvis (65%), skull (29%) and spine (27%) were the most common pagetic localizations. Deafness was present in 12.5% and 65% had hip involvement. 44% patients had been treated with another biphosphonate agent previously. Response rates were 97.9% at 1 year, 87.2% after 2 years and 95.1% after 3 years. The mean ALP levels before ZA infusion was 290 UI/L and after 112 UI/L. Sixteen patients needed a re-treatment in the period of follow up, minimum of 1 year after the ZA infusion and maximum of 8 years after. 56.3% due to raised of ALP levels and 43.8% due pain/ hip involvement. Four patients needed a third infusion due to hip involvement, and 2 of them a forth infusion due to the same reason. All of the patients re-treated due to hip involvement had severe hip involvement at time of diagnosis. In our population, 2 patients achieved 10 years remission, 5 patients 9 years remission and 10 patients 8 years remission with a single ZA infusion. Recording adverse effects were: 14.6% Flu like symptoms (7 patients), 2% assintomatic hypocalcemia (1 patient) and no reports of osteonecrosis or fractures. All of these effects were reported after the first ZA infusion. Conclusions In our population, we find high long-term sustained remission rate. Only sixteen patients needed re-treatment. Patients maintained sustained remission up to 10 years of a single ZA infusion. Incidence of adverse events was similar to the reported in the literature. References Reid IR, Miller P, Lyles K et al. Comparison of a Single Infusion of Zolendronic Acid with Risendronate for Pagets Disease. N Eng J Med. 2005 Set:353(9):898–908 Reid IR, Brown JP, Levitt N et al. Re-treatment of relapse Pagets disease of bone with zolendronic acid: results from an open-label study. Natur BoneKEy Report 2. 2013 Nov: 442: 1–3 Reid IR, Lyles K, Brown JP et al. A Single Infusion of Zolendronic Acid Produces Sustained Remissions in Paget Disease: Data from 6.5 years, JBMR. 2011 Sep 26 (9):2261–70 Devogelaer JP, Geusen P, Daci E et al. Remission over 3 years in patients with Paget disease of bone treated with a single intravenous infusion of 5 mg zolendronic acid. Calcif Tissue Int. 2014 Mar:94(3):311–8 Disclosure of Interest None declared

AB1072 Work Disability, Productivity, Presenteeism and Absenteeism in Rheumatic Patients

Background Work capacity is primarily assessed by absenteeism and rheumatic patients may experience decreased productivity as well as presenteeism due to their health problems as well as its costs consequences. Objectives To evaluate the relation between work disability, productivity and disease activity, quality of life and functional disability. Methods 242 rheumatic patients were recruited, 33.3% employed (N=81) completed the questionnaires of work disability and productivity: WALS (Workplace Activity Limitations Scale), SPS 6 (Stanford Presenteeism Scale) and WPAI (Work Productivity and Activity Impairment) 4 scores - absenteeism, presenteeism, work and activity impairment. Patient-reported parameters included pain, fatigue, sleep quality and disease activity (VAS). Functional disability and quality of life outcomes were assessed by HAQ-DI, FACIT and SF-12. Data were collected during a 4-week period. The analysis included descriptive statistics, Mann-Whitney test and Spearman correlation, p <.05. Results 81 gainfully employed patients (85% female) had 48±11 years old, with 10±4 schooling years. Mean VAS were: pain 47±32, fatigue 57±33, sleep quality 46±33 and disease activity 43±30; HAQ-DI: 1.76±0.9, FACIT:17±11 and SF-12: 39±13 in PCS and 43±18 in MCS. Productivity assessment revealed limitations in all measured scores: WALS 8±6 [0-25], SPS 6 12±3 [3-15], WPAI work impairment 29±32%, activity impairment 29±29%, absenteeism 2.1±12.3% and presenteeism 28±32%. WALS was positively correlated to HAQ (r=.657, p<.0001), FACIT (r=.720, p<.0001), both SF12 scores (r>.517, p<.0001), all 4 WPAIs scores (r>.296, p<.01) and inversely with SPS 6 (r= -.341, p=.002). WPAIs scores were all significantly associated to HAQ, FACIT, SF12 PCS and sick leave in the last 12 months (p<.05). SPS 6 was inversely related to HAQ and FACIT scores, WPAI presenteeism, work and activity impairment (p<.05), but not with absenteeism. Pain and fatigue were significantly higher in patients with higher WALS and WPAI scores, in exception to absenteeism, and pain was associated with SPS 6 (p<.05). Sleep quality was decreased when related to higher WALS and WPAI scores (p<.05). When comparing the employed/unemployed patients, WPAI activity impairment, PCS, MCS, HAQ, FACIT, pain and disease activity (p<.01), we verified significantly higher limitations and impairment in the unemployed group, in exception to SPS 6, fatigue and sleep quality. Conclusions These findings suggest the significant impact of rheumatic disease in productivity losses, and that unemployed patients present worst quality of life and higher levels of pain, fatigue and disability. We found good correlations between the productivity assessment and the SF12, HAQ, FACIT, pain, fatigue, sleep quality and disease activity. This provides information about trend of work restrictions, useful in cost-effectiveness analysis for example of new treatment therapies. Moreover, these issues are particularly important because absenteeism and presenteeism have strong links to health related costs. Prevention of work disability and job changes/adaptations to the individual capabilities would be most effective in reducing socioeconomic and work related impact. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5488

SAT0494 Protein Intake and Body Composition Relationship in A Rheumatic Patient Population

Background The relationship between protein dietary intake and Bone Mass Index (BMI) is controversial. Hyperproteic diet increases urinary calcium excretion but without obvious impact in Osteoporosis (OP). Sarcopenia in the elderly may be associated with low protein diet. High BMI and with high fat content was considered a protective factor for OP but it may be related to vitamin D deficiency and subclinical hyperparathyroidism. Objectives This study aims to evaluate the relationship between protein diet intake, BMI and and parathyroid hormone (PTH) levels. Methods A questionnaire on dietary protein intake was applied to patients at a Rheumatology clinic during 4 non-consecutive weeks from July to September 2013. Nutritional evaluation included body composition (InBody 720). Clinical data collected included: fall occurrence; history of clinical and/or radiologic vertebral fractures; total serum protein, albumin, inorganic phosphate, calcium, PTH, vitamin D and calcium urinary excretion levels and neck/lumbar densitometry. Descriptive statistics, Mann-Whitney, Kruskal-Wallis, Qui-Square and Spearman correlation were applied for a significance of p<0,05. Results 189 subjects were enrolled, 88% female, mean age 58 years, mean BMI 27kg/m2 (low weight in 1,7%, normal in 33,1%, overweight in 37,7% and obesity in 27,6%). Regarding protein intake, 66,7% drunk milk >5 times/week and 22,2% >2 glasses/day; 61,3% of the patients consumed yogurt 1-3 times/day and 20,6% <1/week; 44% consumed cheese once a day. Lean and fatty fish were consumed weekly in 75% of the subjects and canned fish in up to 86%. Codfish and eggs consumption varied between 1 to 4 times/week in 68% and 77%, respectively. Red meat ingestion was: 2-4 times/week in 51%, <3 times/month in 27%. We found an association between weight (r=-0,131;p=0,043), body fat content (r=-0,174;p=0,007) and higher ingestion of lean fish. Patients with lower body fat content had a higher milk intake (r=-0,274;p=0,001). Higher consumption of red meat was associated with higher muscle mass and protein content (r>0,142;p<0,033). We also found a relation between higher PTH and higher BMI (r=0,310;p=0,034). Conclusions Patients that had a lower BMI and reduced body fat content consumed more lean fish, also those with lower body fat content showed a higher intake of milk. Red meat was associated with higher muscle mass and protein content. High PTH levels were correlated with higher BMI, which is in concordance with new evidence suggesting that overweight and obesity do not protect against OP. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5279

SAT0475 Serum Protein Levels, Fall Occurrence, Bone Fractures and Nutrition in Rheumatic Patients – is There Any Relationship?

Background Regardless of epidemiologic evidence suggesting a positive impact of protein dietary intake over bone health, the connection between dietary protein and bone metabolism remains controversial. A hyperproteic diet is linked to increased renal calcium excretion but there is no clear evidence of its relevance in the development of osteoporosis (OP). In the elderly, it is often found a low dietary protein intake and association between low serum albumin levels, femoral neck fracture and post-fracture mortality. A correlation between body composition and fall occurrence is under discussion. Objectives To study the relation between nutritional/biochemical variables and occurrence of falls and fractures. Methods A questionnaire on dietary protein intake was applied to patients at a Rheumatology clinic during 4 non-consecutive weeks from July to September 2013. Nutritional evaluation included body composition (InBody 720). Clinical data collected included: fall occurrence; history of clinical and/or radiologic vertebral fractures; total serum protein, albumin, inorganic phosphate, calcium, parathyroid hormone, vitamin D and calcium urinary excretion levels and neck/lumbar densitometry. Descriptive statistics, Mann-Whitney, Kruskal-Wallis, Qui-Square and Spearman correlation were applied for a significance of p<0,05. Results 196 subjects were included, 88% female, mean age 58 years. The most prevalent rheumatic diseases were: rheumatoid arthritis (RA), osteoarthritis (OA), Sjögrens syndrome, undifferentiated connective tissue disease, spondyloarthritis, systemic lupus erythematosus (SLE) and fibromyalgia. The average body mass index (BMI) was 27,5 kg/m2, higher in patients diagnosed with SLE, OA and RA. 20 subjects (10,2%) had previous history of fall occurrence, 24 (12,2%) had history of fractures (7 vertebral, 2 femoral neck, 4 wrist). We found correlation between the occurrence of fractures and female gender (25 vs. 0 patients, p=0,046); lower T-score at femoral neck (r=-0,521, p=0,046) and lower total serum protein levels (6,39 vs. 6,69, p=0,018). These variables were also correlated with the number of fractures. Fall occurrence was higher in older subjects (64,8 vs. 57,4 years, p=0,017), and in those with higher T-score at lumbar spine (r=0,663, p=0,014). In subjects over 58 years, we found an association with body percentage and BMI, independent of muscle mass (p<0,05). There were no differences between the groups with and without fracture concerning nutritional parameters or mean age (62 vs.57,7 years, p=0,136). Conclusions In this population, in a rheumatologic setting, fractures were commoner in women, with lower bone mineral density and lower serum protein levels. Higher BMI and body fat percentage may be risk factors for fall occurrence in the elderly, eventually related to a shift in the centre of gravity. Nutritional advice in OP patients should consider these notions. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4357