L. Navarini

Polyunsaturated fatty acids: any role in rheumatoid arthritis?

BackgroundPolyunsaturated fatty acids (PUFAs) are members of the family of fatty acids and are included in the diet. Particularly, western diet is usually low in n-3 PUFAs and high in n-6 PUFAs. PUFAs play a central role in the homeostasis of immune system: n-6 PUFAs have predominantly pro-inflammatory features, while n-3 PUFAs seem to exert anti-inflammatory and pro-resolving properties. Rheumatoid arthritis (RA) is a chronic inflammatory arthritis in which many inflammatory pathways contribute to joint and systemic inflammation, disease activity, and structural damage. Research on PUFAs could represent an important opportunity to better understand the pathogenesis and to improve the management of RA patients.MethodsWe searched PubMed, Embase, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI and Wanfang to identify primary research reporting the role of n-3 PUFAs in rheumatoid arthritis both in humans and in animal models up to the end of March 2017.ResultsData from animal models allows to hypothesize that n-3 PUFAs supplementation may represent an interesting perspective in future research as much in prevention as in treating RA. In humans, several case-control and prospective cohort studies suggest that a high content of n-3 PUFAs in the diet could have a protective role for incident RA in subjects at risk. Moreover, n-3 PUFAs supplementation has been assessed as a valuable therapeutic option also for patients with RA, particularly in order to improve the pain symptoms, the tender joint count, the duration of morning stiffness and the frequency of NSAIDs assumption.Conclusionsn-3 PUFAs supplementation could represent a promising therapeutic option to better control many features of RA. The impact of n-3 PUFAs on radiographic progression and synovial histopathology has not been yet evaluated, as well as their role in early arthritis and the combination with biologics.

The relation between, metabolic syndrome and quality of life in patients with Systemic Lupus Erythematosus

Introduction Systemic Lupus Erythematosus (SLE) is associated to an increased prevalence of Metabolic Syndrome (MeS) and to a reduction of Quality of Life (QoL). The aim of this study is to evaluate the association between MeS and QoL in SLE. Methods SLE patients were consecutively enrolled in a cross sectional study. MeS was defined according to IFD definition. Therapy with glucocorticoids (GC) and antimalarial was analyzed as cumulative years of exposure. We used a cut off of 7.5 mg of prednisone to define high daily dose of GC. QoL was quantified using SF-36. We used BDI and HAM-H to assess symptoms of mood disorders. Fatigue was evaluated using Facit-Fatigue, physical activity using IPAQ, sleep quality using PSQI and alexithymia using TAS-20. Results We enrolled 100 SLE patients. MeS prevalence was 34%. Patients with MeS presented reduced scores in SF-36 MCS and PCS compared to patients without MeS (p 0.03 and p 0.004). BDI and HAM-H score were significantly higher in patients meeting MeS criteria compared to subjects without MeS (p 0.004, p 0.02). These results were confirmed after adjustment for confounders. Compared to patients without MeS, those with MeS presented higher age, lower education level, higher recent SELENA-SLEDAI, higher number of flares, increased SDI, longer cumulative exposure to high dose GC and shorter duration of antimalarial therapy. In the multiple logistic regression model, the variable associated to the Odds Ratio of having MeS were: the average of recent SELENA-SLEDAI (OR 1.15 p 0.04), the years of exposure to high dose of GC (OR 1.18 p 0.004), the years of exposure to antimalarials (OR 0.82 p 0.03) and the BDI score (OR 1.1 p 0.005). Conclusion A modern management of SLE should not miss to take all the possible measures to ensure an adequate QoL to SLE patients, with particular attention to those affected by MeS.

Role of the Specialized Proresolving Mediator Resolvin D1 in Systemic Lupus Erythematosus: Preliminary Results

Objective Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and its pathogenesis has not yet been completely clarified. Patients with SLE show a deranged lipid metabolism, which can contribute to the immunopathogenesis of the disease and to the accelerated atherosclerosis. Resolvin D1 (RvD1), a product of the metabolism of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), acts as a specialized proresolving mediator which can contribute in restoring the homeostasis in inflamed tissues. The aim of the present pilot study is to evaluate plasma levels of RvD1 in patients with SLE and healthy subjects, investigating its potential role as a biomarker of SLE and assessing its relationship with disease activity and laboratory parameters. Methods Thirty patients with SLE and thirty age- and sex-matched healthy subjects (HSs) have been consecutively recruited at Campus Bio-Medico University Hospital. RvD1 plasma levels were measured by ELISA according to the manufacturers protocol (Cayman Chemical Co.). RvD1 levels were compared using Mann–Whitney test. Discriminatory ability for SLE has been evaluated by the area under the ROC curve. Results Lower levels of RvD1, 45.6 (35.5–57.4)u2009pg/ml, in patients with SLE have been found compared to HSs, 65.1 (39.43–87.95)u2009pg/ml (p = 0.0043). The area under the ROC curve (AUC) for RvD1 was 0.71 (95% CI: 0.578–0.82) and the threshold value of RvD1 for the classification of SLE was <58.4u2009pg/ml, sensitivity 80% (95% CI: 61.4–92.3), and specificity 63.3% (95% CI: 43.9–80.1), likelihood ratio 2.2 (95% CI: 1.3–3.6). Conclusions The present preliminary study allows hypothesizing a dysregulation of RvD1 in patients with SLE, confirming the emerging role of bioactive lipids in this disease.

Leptin in autoimmune mechanisms of systemic rheumatic diseases

In the last two decades, white adipose tissue (WAT) has been recognized as a key actor of many physiological and pathological conditions. WAT is able to produce mediators, named adipokines, which may affect systemic homeostasis. In particular, leptin is not only involved in appetite and energy metabolism, but also in immune system. Increasing evidence established that leptin can regulate both innate and adaptive immunity mainly with pro-inflammatory effects but also, to a lesser extent, with anti-inflammatory features. In autoimmune diseases, a failure or breakdown of the mechanisms of self-tolerance is observed. Leptin, which plays an important role in the control of immune balance, has been involved in autoimmunity generation and maintenance. In this review, it has been provided an up-to-date report about the role of leptin in systemic autoimmune diseases, with particular reference to connective tissue diseases, inflammatory arthritis, and vasculitis.

AB0046 Endocannabinoid System and Systemic Lupus Erythematosus

Background Endocannabinoid (eCB) system comprises endogenous lipid mediators (eCBs) like N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), along with their specific G protein-coupled type-1 (CB1) and type-2 (CB2) cannabinoid receptors, and the proteins responsible for eCB biosynthesis, inactivation, transport, and accumulation. In recent years, many studies have evaluated the role of eCBs in the homeostasis of the immune system. Notably, AEA and the eCB-like molecule N-palmitoylethanolamine (PEA) seem to be anti-inflammatory mediators, while 2-AG is implicated in both pro-inflammatory and anti-inflammatory functions. Moreover, the effects of eCBs on immune system seem to be mostly mediated by CB2, more expressed in immune cells than by CB1. The latter receptor, instead, is more implicated in neurotransmission. Several studies have already investigated the role of eCB system in different immune-mediated diseases, such as multiple sclerosis and type-1 diabetes. Objectives To investigate the role of eCB system in patients with systemic lupus erythematosus (SLE) and age and sex matched healthy subjects. Methods 10 female patients with SLE and 10 healthy subjects were enrolled from outpatient clinic of Campus Bio-Medico University of Rome. Every SLE patient was positive for anti-dsDNA antibodies and/or exhibited hypocomplementemia with or without hypergammaglobulinemia, ENA or aPL positivity. None of them was treated with biological therapy at the time of enrolment, nor with steroid bolus in the previous six months, while treatment with conventional immunosuppressants was allowed. SELENA-SLEDAI and BILAG were used to assess disease activity and SDI as damage index. AEA, 2-AG and PEA levels were quantified in plasma of SLE patients and healthy controls by using liquid chromatography-tandem mass spectrometry (LC-MS). Results No significant difference among ages was found in the two groups (SLE patients 37.9±5.9 years, healthy subjects 37.8±6.2, p=ns). In SLE patients, 80% of the subjects exhibited low C3, 50% low C4, 90% anti-dsDNA positivity; 30% of them were not taking glucocorticoids, 20% ≤5 mg of daily prednisone and 50% >5 mg of daily prednisone; 70% were taking conventional immunosuppressive treatment and 80% were taking hydroxychloroquine. Value of the disease activity score evaluated by SELENA-SLEDAI was assessed as 6±4.7; 10% of the patients exhibited at least 1 BILAG A and 60% at least 1 BILAG B; value of the damage index evaluated by SDI was assessed as 0.6±0.8. eCBs was significantly altered in SLE patients. In particular, plasma levels of 2-AG were significantly increased in SLE patients compared to healthy controls (p=0.005), while no differences were found in AEA and PEA concentrations between the two groups. Conclusions Our results demonstrate, for the first time, an alteration of eCB system in SLE patients; these data may help to better understand the role of lipid mediators in SLE pathogenesis. References Fezza F. et al. Molecules. 2014; 19:17078–106. Gruden G. et al. Br J Pharmacol. 2015. doi: 10.1111/bph.13226 Disclosure of Interest None declared

AB0341 Rheumatoid Arthritis Associated Interstitial Lung Disease Progression in a Cohort of Treated to Target Patients

Background Interstitial lung disease (ILD) is the most common manifestation of rheumatoid lung disease (RA-ILD). The prevalence of RA-ILD is somewhere between 10 and 50 percent, depending on the study. In analogy with Systemic Sclerosis associated ILD (SSc-ILD), high resolution computed tomography (HRCT) has become the gold standard for diagnosis of RA-ILD. Literature data describe a strong correlation between HRCT pattern of ILD and histopathological subtypes. Moreover, different systems for evaluating SSc-ILD on HRCT and several scoring methods have been proposed for RA-ILD. Because of the uncertainty of the effect of traditional DMARDs and biologic agents on the development and course of ILD in patients with RA, careful pre-treatment assessment and subsequent monitoring are required. We present the results of the follow-up to 1 year of a cohort of patients treated with DMARDs and maintained in the therapeutic target (DAS28 low disease activity or remission). Objectives To evaluate the change in respiratory function and ILD HRTC score in a cohort of patients treated to target. Methods 24 RA patients in DMARD monotherapy and low dose steroid (dose of prednisone <7.5 mg/die), followed by treat-to-target strategy and kept in DAS28 low disease activity or remission, were enrolled. All patients were evaluated with pulmonary function tests (global spirometry, DLCO and hemogasanalysis) and HRCT at time of the enrollment and after 1 year of follow-up. All HRCT examinations were performed according to standard protocol. The parenchymal abnormalities on HRCT were coded and scored in all the images by two independent readers, blinded with respect to the results, according to Warrick et al. The severity and extent of disease were then calculated as total HRCT score (range from 0 to 30). Results 19 of 24 patients were in MTX monotherapy (mean MTX weekly dose: 12.5 mg) and 5 were in Leflunomide monotherapy. Mean RA disease duration was 4.8 yr (±0.6 SD). 20 of 24 patients presented HRCT signs of ILD with Warrick score ≥1. At time 0 mean HRTC score was 8 (±5 SD), mean extension score was 4 (±2 SD) and mean severity score was 4 (±3 SD). At time 1 yr mean HRTC score was 8,04 (±3,73 SD), mean extension score was 3,37 (±1,86 SD) and mean severity score was 4,66 (±2,11 SD) (p=NS). Mean DLCO was 74 (±21 SD) at time 0 and 66 (±18 SD) at the end of follow-up (p=NS). We found no statistically significant modification in total lung capacity (TLC) and Tiffenau index (FEV1/FVC) during follow-up. Conclusions As previously reported, we found high prevalence of RA-ILD. In our treated-to-target RA cohort in DMARD monotherapy, we have not detected neither functional nor radiological progression during 1 year follow-up. In our cohort the DMARD therapy has not worsened the ILD. We can speculate that control the activity of joint disease with a strategy to treat target may contribute to prevent lung disease progression. Disclosure of Interest None declared

SAT0542 Musculoskeletal Syndromes Related to Aromatase Inhibitor Therapy: A Clinical and Laboratory Evaluation

Background Aromatase inhibitors (AI) are widely used in the treatment of estrogen receptor-positive breast cancer in postmenopausal women. The onset of musculoskeletal symptoms related to AI therapy limits the treatment compliance. Objectives To evaluate the incidence and the clinical presentation of musculoskeletal syndromes and the prevalence of autoantibodies during AI therapy. Methods We enrolled 49 consecutive postmenopausal patients with non-metastatic breast cancer treated with third generation AI for at least three months (AI+ group) and 10 postmenopausal controls with breast cancer in adjuvant therapy but not treated with AI (AI- group). The two groups were evaluated with a rheumatological examination (tender and swollen joint count, tender points, CDAI), with PRO-CLARA, FACIT-fatigue and HAQ questionnaires and ANA, ENA screen and ACPA dosage. ANA were assayed in indirect immunofluorescence on Hep-2 cells using as a cut-off a dilution of 1:80; ENA screen and ACPA were assayed with ELISA commercial kits. Results The mean ages were 62.6±9 years for AI+ group and 58±11.8 years for AI- group (p=0.2, U=140.5). In AI+ group, 27 (55%) patients exhibited at least one tender joint and 15 (30%) patients exhibited at least one swollen joint. In AI- group, two patients exhibited at least one tender joint and one patient exhibited at least one swollen joint. 22% of AI+ group patients and 20% of AI- group patients showed more than 11 tender points (TP). When patients with more than 11 TP positivity were excluded from the analysis, tender joint count was more higher in AI+ group (p=0.037). Differences between AI+ and AI- groups regarding PRO-CLARA, FACIT-fatigue, HAQ and CDAI were summarized in Tab. 1. In AI+ group, PRO-CLARA values correlates with FACIT-fatigue values (R=-0.59, p<0.0001), swollen joint count (R=0.48, p=0.001), tender joint count (R=0.72, p<0.0001), tender points count (R=0.76, p<0.0001), HAQ values (R=0.85, p<0.0001), CDAI values (R=0.89, p<0.0001) and does not correlate with the age of the patients. 67% of the AI+ group patients showed ANA positivity vs 20% AI- group patients (p 0.01, RR 3.3).Table 1 AI+ group AI- group p PRO-CLARA 2.65±2.15 1.56±2.39 p 0.048 FACIT-fatigue 38±9 39±8 p 0.58 HAQ 0.750 0.3 p 0.030 CDAI 7±6 2±3.5 p 0.005 Conclusions In this preliminary study, we demonstrated a higher prevalence of arthralgia/arthritis in AI+ group than in AI- group. No significant difference in tender points count was detected between the two groups. In AI+ group, higher values of PRO-CLARA, HAQ and CDAI than those of AI- group were showed. A higher rate of ANA positivity was demonstrated in AI+ group. These results support the hypothesis of a possible role of an immune system dysregulation in the development of musculoskeletal syndromes during AI therapy. The expertise of a rheumatologist could help patients with estrogen receptor-positive breast cancer treated with AI to improve their quality of life and to ensure a greater compliance to AI therapy. References Lønning PE, et al. Endocr Relat Cancer. 2013 Jun 24;20(4):R183-201. Niravath P. Ann Oncol. 2013 Jun;24(6):1443-9. Shanmugam VK, et al. Breast Cancer Res Treat. 2012 Jan;131(2):699-708. Disclosure of Interest None declared

Utility of ultrasound in the diagnosis of chronic worsened gout

Ultrasound (US) may be used to diagnose chronic worsened gout. US confirmed the clinical evidence of tophaceous deposits in the left elbow of a 75-year-old man; it also identified crystalline materials on the cartilage surface of the second metacarpophalangeal joint of the left hand. US may be helpful to detect signs of deposition of monosodium urate crystals in periarticular and intra-articular joints of patients with clinically suspected chronic worsened gout.