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Rheumatoid arthritis is a systemic, chronic disease which may increase the risk of osteoporosis. This study was carried out in order to examine the effect of conjugated linoleic acid (CLA) on bone markers in rheumatoid arthritis disease which is the most common autoimmune disease. The present study is a randomized double-blind clinical trial. Subjects included 52 patients with active rheumatoid arthritis who were divided into two groups. Group I received standard treatment plus 2 daily 1.25 g capsules (Containing about 2 g of 9- cis 11- trans isomer and 10- cis 12- trans isomer in ratio of 50 −50 CLA in glycerinated form), Group II received standard treatment plus 2 Placebo 1.25 g capsules containing sunflower oil with high oleic acid. Telopeptides C, osteocalcin, and MMP3 were analyzed by ELISA method, PGE 2 was done by competitive enzymatic immunoassay method, and IGF-1 was analyzed by the IRMA method based on the sandwich method and ALK-P of bone. Before and after the intervention, the questionnaires about general information, nutrition assessment and medical history were filled out by the subjects. Nutritional assessment was done by a 24-h record questionnaire for the three-day diet. The results were analyzed using SPSS software (version 18). Findings: There was no significant difference between the groups in enzyme activity of ALK-P of bone, PGE 2 and MMP3 variables. However, differences between the two groups in terms of activity of telopeptides C, Osteocalcin, and IGF1 were significant ( P  < 0.05). CLA has a potentially beneficial effect on bone markers in patients with rheumatoid arthritis. Therefore, in order to study the effect of CLA on bone health in patients with RA and all patients with autoimmune and bone diseases more studies with longer duration and evaluation of bone mass density are required.

BackgroundBehçet’s syndrome (BS) is an autoinflammatory disease characterized by a variable vessel vasculitis. In children, BS may start early in life, mimicking other autoinflammatory diseases and making the diagnosis challenging. In the past, several criteria have been created for adult BS classification. In 2015, the first set of BS paediatric classification criteria, the PEDBD, was proposed by an international Expert consensus [1].Objectivesto perform an external validation of the PEDBD criteria in a cohort of internationally validated paediatric BS patients.Methods210 patients (70BS, 40 PFAPA, 35 FMF, 26 MKD, 22 TRAPS, 17 UND/ SURF) were randomly selected from the Eurofever Registry (patients excluded if > 16 years and if included in first PEDBD study). A set of 11 Experts blinded to original diagnosis, were chosen to evaluate the patients: in the 1st round, clinical and serological data were evaluated; in the 2nd round genetic data were added; in the 3rd round the other Experts’ votes and comments were shown. Using the expert consensus as gold standard (agreement>80%), the PEDBD, the ISG and the ICBD criteria were applied to BS patients and to the confounding diseases in order to define the sensitivity, specificity and accuracy.ResultsAt the end of the 3rd round, a consensus on the initial diagnosis was reached in 112/210 patients (53.3%), with an additional consensus on a different final diagnosis in 27 patients. The BS patients with an agreement (24) were classified as confirmed-BS, and those with an agreement of 60-70% (10) as probable-BS. In confirmed-BS patients, oral ulcers were present in all the patients, genital ulcers in 77%, skin manifestations in 50%, a positive pathergy reaction in 39%, anterior and posterior uveitis in 29 and 27%, retinal vasculitis and papillary oedema in 8% of patients, with a resulting impaired vision in 17%. Venous thrombosis was present in 2 patients (8%). The patients with ocular and vascular involvement were all males. Cranic nerve palsy (17%) was the most frequent neurologic symptom. Abdominal pain was present in 33%, diarrhoea and gastrointestinal bleeding in 13% and anal/perianal ulcers in 8%. 29% presented arthralgia, and 13% arthritis. Fever was present in 50% of patients. HLA-B51 was positive in 69% of patients.When comparing these patients with the confounding diseases, an older age at disease onset, the presence of oral and genital ulcers, skin papulo-pustular lesions, a positive pathergy test and posterior uveitis were BS distinctive elements. The ISG, ICBD and PEDBD criteria were applied to confirmed and probable-BS and to the confounding disease controls, resulting in the following test characteristics (Table 1).Table 1.CriteriaSensitivitySpecificityAccuracyISG0.501.00.90ICBD0.790.980.95PEDBD0.580.990.91Conclusionthe PEDBD criteria were extremely specific but had a lesser sensitivity than ICBD which had a better accuracy. One limitation is that specific monogenetic BS mimics were not included as disease controls, thus the true accuracy of all these criteria may be lower in practice. The complexity of childhood BS suggests that genotyping (incorporating autoinflammatory diseases, BS mimics, and HLA-type) combined with clinical features are likely to yield the most accurate classification criteria, which would require further validation in a larger cohort.Reference[1]Koné-Paut I et al. Consensus classification criteria for paediatric Behçet’s disease from a prospective observational cohort: PEDBD. Ann Rheum Dis. (2016) 75:958–64. doi: 10.1136/annrheumdis-2015-208491Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundA remarkable variability in the clinical course of Behçet’s Syndrome (BS) seems to arise by comparing cohorts from different geographical areas. However, no data are currently available on the possible variability of organ damage burden, although it is currently recognized as a major outcome in BS.ObjectivesTo evaluate and compare the extent, characteristics, and associated factors of organ damage in patients from different World areas.MethodsWe analyzed demographic and clinical data of a multicenter cohort of 935 consecutive BS patients from 11 Countries clustered in 5 geographic areas: Europe (EU, n 345), North Africa (NA, n 278), Middle East (ME, n 227), Central Asia (CA, n 44), America (AM, 41). Organ damage was assessed by the BS organ damage index (BODI) [1]. Uni- and multivariate analysis was performed to evaluate the association between the geographical region and organ damage using demographic and clinical data as covariates.ResultsDemographics and clinical features are reported in the Table 1. The prevalence of any damage (BODI≥1) in the EU, ME, NA, CA, and AM areas was 47.0%. 54.6%. 91.7%. 97.6% and 77.3%, respectively, whereas the mean (SD) total BODI score was 1.1 (1.7), 1.2 (1.7), 3.5 (2.4), 4.5 (2.6), and 1.9 (1.9). The prevalence of different BODI domains is reported in the Table 1. Significant differences were recorded in NA vs. EU and ME cohorts (Figure 1) (CA and AM not included in the statistical analysis for the small sample size). In multivariate analysis, the geographical area was independently associated (p < 0.001) with damage (NA vs. EU OR 11.3; ME vs. EU OR 1.5). Male gender (OR 1.5; p = 0.004), age (OR 1.03 per year; p = 0.002), disease duration (1.03 per year; p = 0.003), ocular (OR 2.8; p <0.001), vascular (OR 5.3, p <0.001), and neuropsychiatric (OR 3.8, P<0.001) involvement were also associated with BODI≥1.ConclusionA variable prevalence of organ damage was observed in BS patients from different World areas. Further research is needed to understand the cause underlying such geographic variability, as it may unveil biological, environmental, or health-system factors driving damage accrual in BS. The BODI effectively captures damage independently from the studied cohort’s geographical origin.Reference[1]Piga M. Floris A. Espinosa G. et al. Development and preliminary validation of the Behçet’s syndrome Overall Damage Index (BODI). RMD Open 2020;6:e001192.Table 1.Demographic and clinical characteristic of the patients form different geographical area.EuropeMiddle EastNorth AfricaCentral AsiaAmericaMales37.1%59.5%80.2%41.5%40.9%Age, yrs46.3 (14.1)37.4 (10.0)37.7 (11.1)36.2 (17.6)44.1 (14.5)Disease duration, yrs14.6 (11.4)12.1 (8.7)8.6 (7.2)11.6 (9.6)14.3 (10.1)Diagnosis delay, yrs4.1 (7.2)6.5 (7.4)2.4 (4.8)5.2 (6.1)4.5 (6.5)BODI domainsMucocutaneous13.0%14.5%46.8%92.7%4.5%Musculoskeletal3.2%0.4%1.4%7.3%6.8%Ocular22.0%31.3%54.3%68.3%31.8%Vascular10.7%12.3%36.0%7.3%18.2%Cardiovascular11.9%12.3%37.4%12.2%18.2%Neuropsychiatric11.3%4.8%18.3%46.3%36.4%Gastrointestinal0.6%1.3%1.4%0.0%0.0%Miscellaneous10.4%5.3%4.0%9.8%9.1%BODI score1.1 (1.7)1.2 (1.7)3.5 (2.4)4.5 (2.6)1.9 (1.9)In males1.6 (2.1)1.5 (1.8)3.7 (2.3)5.0 (2.9)2.9 (2.2)In females0.8 (1.3)0.9 (1.4)2.6 (2.4)4.2 (2.5)1.7 (1.8)Europe included patients from Italy. Portugal. Spain. Greece; North Africa: Morocco. Egypt; Middle East: Turkey. Iran; Central Asia: Kazakhstan; America: USA. Brazil. Continuous variables are reported as mean (SD).Acknowledgements:NIL.Disclosure of InterestsNone Declared.

•Waist and hip circumference significantly were decreased in the intervention group, but there wasnot significant differences between two groups.•Body fat percent, low density lipoprotein levels and systolic blood pressure significantly were decreased in the intervention group.•A significant decrease was observed in body fat percent, hip circumference, fasting blood sugar and high density lipoprotein in the intervention group compared to the placebo group. Since, the main cause of death in Rheumatoid arthritis (RA) patients is the presence of type 2 diabetes, abnormal increase in blood lipids, blood pressure and obesity, the aim of this study was to assess the effects of Barberry on the anthropometric indices and metabolic profile in patients with RA. present study was a double-blinded, placebo-controlled randomized clinical trial. 70 active RA patients were randomly allocated into intervention or placebo group Participants received 6 capsules of 500 mg barberry extract or placebo for 3 months. Serum levels of fasting blood sugar (FBS), triglyceride (TG), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), systolic and diastolic blood pressure and anthropometric factors were assessed at baseline and at the end of the trial. The results of intervention on 62 patients showed that weight, BMI, and conicity index increased in both groups, but this was significant only in the placebo group (p < 0.001). Waist and hip circumference were decreased in the intervention group and increased significantly in the placebo group (p < 0.001). Body fat percent (p = 0.04), LDL-C (p = 0.05) and SBP (p = 0.02) significantly were decreased in the intervention group. The results showed a significant decrease in body fat percent (p = 0.05), hip circumference (p < 0.001), FBS (p = 0.03) and HDL-C (p = 0.03) in the intervention group compared to the placebo. Conclusions: Overall, the results of this study demonstrated that the extract of Berberis Integerrima had beneficial effects on metabolic profile and anthropometric indices in RA patients.

Background Little information on the effects of Vitamin E on inflammation and immune function in humans is available so we decided to investigate the effect of Vitamin E on this autoimmune disease, as our knowledge for the first time. Objectives This study investigated the effects of Vitamin E on the inflammatory mediators and Immunity factors in adults with active RA Methods In a randomized, double-blind, placebo controlled clinical trial 43 RA patients were randomly divided into 2 groups, each group receiving one of the following daily supplement for 3 months; Group E: 400 mg Vitamin E, Group P: placebo. Cytokines, Citrolinated Antibody (CCP-A)were measured by Elisa method, Vitamin E measured by HPLC. Results After study there were no significant differences between groups in cytokines IL2, IL4, TNFα, IL1β, Il2/IL4, CCP-A, WBC and Neutrophils, Lymphocyte, Monocytes, Eeosinophils numbers.TNFα decreased in 2 groups nonsignificantly, but its reduction was more in group E. IL1β increased in both groups P and E (P=0.004, P=0.041 respectively). IL4 decreased in groups E and P (P=0.07, P=0.068 respectively). ESR, CRP, DAS 28 and GPA decreased in group E (P≤0.05). Conclusions Vitamin E probably can be useful in RA patients. References Venkatraman J, Meksawan K(2002) Effects of dietary omega3 and omega6 lipids and vitamin E on chemokine levels in autoimmune-prone MRL/MpJ-lpr/lpr mice. J Nutr Biochem 13(8), 479. Comstock GW, Burke AE, Hoffman SC, Helzlsouer KJ, Bendich A, Masi AT, Norkus EP, Malamet RL, Gershwin ME(1997) Serum Concentration of alpha tocopherol and carotene and retinol perceding the diagnosis of rheumatoid arthitis and systemic lupus erythmatus. Ann Rheum Dis 56, 323- 5. Edmonds SE, Winyard PG, Gue R, et al.(1997) Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis, Results of a prospective placebo controlled double blind trial. Ann Rheum Dis 56, 649-55. Tidow -Kebritchi S, Mobarhan S (2001). Effects of diets containing fish oil and vitamin E on rheumatoid arthritis. Nutr Rev 59(10), 335-8. Wittenborg A, Petersen G, Lorkowski G, Brabant T(1998) Effectiveness of vitamin E in comparison with diclofenac sodium in treatment of patients with chronic polyarthritis. ZRheumatol 57(4), 215-21. J van Tits L, Demacker P N, Graaf Jde, Lemmers H LH, Anton F (2000)α-Tocopherol supplementation decreases production of superoxide and cytokines by leukocytes ex vivo in both normolipidemic and hypertriglyceridemic individuals. Am J Clin Nutr 71, 458–64. Pallest EG, Schoten EG, Dewaart FG, Fonk HC, Doekes G (1999) Effect 50 and 100 mg vitamin E supplements on Cellular immune function in noninstitutionalized elderly person.American Journal of Clinical Nutrition 69(6),1273-81. Beharka AA, Wu D, Serafini M, Meydani SN(2002) Mechanism of Vitamin E inhibition of Cyclooxygenase activity in macrophages of old mice role of peroxynitrite. Free Radic Biol Med 15, 32(6), 503-11. Disclosure of Interest None Declared

Little information about the effects of conjugated linoleic acids (CLAs) on inflammation and immune function in humans is available. This study investigated the effects of CLAs, with and without Vitamin E on immunity and inflammatory parameters in adults with active rheumatoid arthritis (RA). In a double-blind clinical trial, 78 patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months; group C: 2.5 g CLAs, group E: 400 mg Vitamin E, group CE: CLAs plus Vitamin E, group P: Placebo. Cytokines, matrix metalloproteinase 3 (MMP-3) and citrullinated antibody (CCP-A) were measured by ELISA method and Vitamin E by high-performance liquid chromatography. Consider statistical methods there were no significant differences between groups in cytokines interleukin-2 (IL-2), IL-4, tumor necrosis factor-α (TNF-α), IL-1β, IL-2/IL-4, CCP-A white blood cells and neutrophils, lymphocyte, monocytes, and eosinophils numbers. TNF-α decreased in all groups, but its reduction was significant in group CE. IL-1β increased in groups P (P = 0.004) and E (P = 0.041) but the difference between group P and CE was significant. IL-4 decreased in groups C, CE and E (P = 0.03, P = 0.03, P = 0.07 respectively). IL2 did not change significantly within groups. CCP-A increased in groups P (P = 0.035) and E (P = 0.05), while it decreased in groups CE (P = 0.034). CCP-A and MMP-3 decrease were significant between groups P and CE. MMP-3 reduction was significant in group CE. Co-supplementation CLAs and Vitamin E may be effective in the level of inflammatory markers in RA patients.

Background BD is rarely encountered in children where the disease is very difficult to recognize. The outcome of patients with few symptoms is currently unknown Objectives To define the outcome of paediatric patients with at least two symptoms of BD, and to obtain an appropriate definition of BD in patients <16y Methods An international expert committee has defined the criteria of inclusion. New patients or patients followed for a maximum of 3 years, who presented at least 2 symptoms of BD (among a list), and gave their informed consent were included, reviewed yearly. Results 223 patients (SR: 1), from 22 centres of 12 countries, were included since 2008, median age of 13,3y (2.3-21y). Median age at first symptom was 8y (9m-18y). Family history of BD was present in 50 (22.4%) and consanguinity in 10 (4.5%). Median disease duration at inclusion was 4.7y (0-16,5y) and from the first symptom to last visit was 5.5y (1m-19.4y). Inclusion criteria plus oral aphtosis (mandatory) were (%): genital aphtosis 51.1, necrotic folliculitis 31.4, uveitis 28.7, familial history 22%, pathergy test positive 18.8, erythema nodosum 14.3, vascular 10 and retinal vasculitis 7.2. Mean number of symptoms: 1 plus family history (41%), 2 (33%), more than 3 (26%). Patient had a median of 1.0 follow-up visit (0-4). 217 patients had a first visit: where symptoms were as follows (%): genital aphtosis 49, skin lesions 49, joints and fever 41, eyes lesions 35, neurological 34.5, gastrointestinal 30.5 and vascular16.5. HLAB51 was present in 48% and A26 in 4%. Male patients had significantly more uveitis. 138 patients had a 1-y visit (mean BD duration: 5.6y). 81 patients had 2-y (6.3y), 44 a 3-y (7.2y) and 18 a 4-y visit (7.4y). Between 1st-4th visit: 62% had no new symptom, 23% had one, and 8% had 2 and 7 had more than 3. The expert committee has reviewed 196 files at a median disease duration of 6,7y (0.9-19y), and classified 118 patients as definite, 21 as probable and 3 as not BD. 54 charts were reviewed but did not reached consensus. 45 files have been reviewed more than once. Although good concordance (Kappa coefficient = 0.72), International criteria and expert classification showed significant differences: 60.2% (118/196) patients were classified as definite BD by experts, whereas only 45.9% of these patients met the international criteria (P<0.0001). Having 2 or more symptoms was significantly associated with classification as definite BD (p=0.0005). Conclusions The expert committee has classified the majority of patients in the BD group although they did not fulfil the international BD classification criteria (for adults) Disclosure of Interest None Declared

Background BD is rarely encountered in patients before 16y where the disease is very difficult to recognize. In addition to the diagnostic challenge, the outcome of patients with few symptoms is currently unknown. Objectives PED-BD is an international database aimed to define the outcome of either paediatric BD patients or patients with at least two symptoms of the disease, in order to propose paediatric criteria for BD. Methods An international expert committee has defined criteria for eligibility in the study. New patients or patients followed for a maximum of 3 years, who presented at least 2 symptoms of BD (among a list), were selected for retrospective and prospective analyses. An eCRF was built and inserted into a secured database (CLeanWeb). Patients included are reviewed yearly and judged as definite, probable or not BD, by an expert committee. Results 206 patients (SR:1), from 22 centres of 12 countries, have been included since 2008, median age 13,5y (2,3-21y). Median age at onset was 8y (9m-18y), family history was 22,3% and consanguinity 4.4%. At inclusion, median disease duration from onset to last visit was 5.5y (1m-19y). The criteria of inclusion in addition to oral aphtosis (mandatory): genital aphtosis 52%, necrotic folliculitis 30%, uveitis 29%, familial history 22%, pathergy positive 19%, erythema nodosum 14,5%, skin ulceration 11%, vascular 8,7% and retinal vasculitis 7%. Number of symptoms: 1 plus family history (42,7%), 2 (30,6%), more than 3 (26,7%). Patient had a median of 1 follow-up visit (0-4). 200 patients had a first visit, symptoms as follows: Skin lesions 58%, joints and fever 41%, eyes lesions 36%, neurological 34%, gastrointestinal 29% and vascular (12%). 84% received treatment: colchicine 59%, steroids 29%, azathioprine 12% and MTX 9%. Male patients had significantly more uveitis. 135 patients underwent first year visit. 62 had no new symptom, 43 had one, and 15 had 2 and 15 had 3. 73 patients had a 2y, 37 a 3y and 17 a 4y visit. The expert committee has reviewed 114 files at a median disease duration of 6,2y (0-18y), and classified 72 patients has definite, 44 as probable and 2 as not BD. Among patients classified as BD: 57 met the international criteria. Symptoms associated with classification as definite were skin (74% of the definite had this symptom), genital aphtosis (67%), eyes (51%) and pathergy (26%). None of the symptoms were observed in patients not classified as definite. The Kappa concordance coefficient between the 2 classifications reached 0.73 with a 95% CI= [0.62-0.86]. Conclusions The PED-BD cohort is characterized by an equal sex ratio, a high rate of familial aggregation, and marked phenotypic differences by gender. In this large series of patients with few symptoms, the expert committee judgments gave higher number of patients classified as BD than the classification by the international classification criteria. Disclosure of Interest None Declared

Objectives To present the clinical characteristics, disease course, management, and outcomes of COVID-19 infection in patients with Behcet’s disease (BD). Methods In this retrospective cohort study, we retrieved BD patients with definite diagnosis of COVID-19 infection. Demographic data, comorbidities, features related both to BD and COVID-19 infection, treatments, and outcomes were collected. Comparisons between patients with or without hospitalization were performed. All statistical analyzes were performed using SPSS version 25. We considered p  < 0.05 statistically significant. Results We identified 61 episodes of COVID-19 infection in 59 BD patients. The prevalence was 0.69%. The median age was 45 years ( IQR  = 20), and the median disease duration was 162 months ( IQR  = 195). BD features were similar except for higher rate of arterial involvement and positive pathergy test in infected patients. Thirty-five episodes (62.5%) happened in non-active patients; 39% had a comorbid disease. COVID manifestations were the same as the general population. Flu-like symptoms were the most common (85%), followed by fever (66%), ageusia/anosmia (56%), headache (51%), and pulmonary involvement (48%). There was no change in BD symptoms in 74%. Fifteen patients (25.4%) were hospitalized, and one patient (1.7%) died. Receiving glucocorticoids ( p  < 0.03) and cytotoxic drugs ( p  < 0.02) were associated with an increased rate of hospitalization. Conclusion The incidence of COVID-19 infection in BD patients was not higher than general population in Iran. They showed milder form of disease with lower morbidity and mortality rate. Most were on immunosuppressive drugs, or had a comorbidity apart from BD. No significant effect on BD course was shown. Key Points • The incidence of COVID-19 infection in patients with Behcet’s disease is not higher. • They showed milder form of infection with lower morbidity and mortality rate. • No significant effect on Behcet’s disease course was shown with COVID19 infection. • BD patients can be managed according to the guidelines used for general population.

Many studies have investigated the possible role of reactive oxygen species in the etiology and pathogenesis of Rheumatoid Arthritis (RA). The aim of this study was to investigate the activities of some antioxidants in RA patients. In this case-control study, 59 RA patients and 60 healthy sex and age-matched controls were selected. Vitamin E and Beta-carotene were determined using HPLC. Erythrocytes glutathione reductase (GR) activity was measured spectrophotometrically, and malondialdehyde (MDA) was determined by colorimetric method. Arylesterase activity (AEA) was measured by Phenylacetate. The clinical data were determined by a rheumatologist, medical history and filling the questionnaire by interview. Statistical analyses were carried out using the SPSS software. In patients with RA, serum MDA level was significantly higher and plasma concentration of vitamin E, Beta-carotene and GR activity, were significantly lower than healthy control (P< 0.001). AEA activity differences between two groups were non-significant. Oxidative stress may play an important role in the inflammation and pathogenesis of RA.