Özlem Pehlivan

Cluster Analysis of Autoantibodies in 852 Patients with Systemic Lupus Erythematosus from a Single Center

Objective. Associations between autoantibodies and clinical features have been described in systemic lupus erythematosus (SLE). Herein, we aimed to define autoantibody clusters and their clinical correlations in a large cohort of patients with SLE. Methods. We analyzed 852 patients with SLE who attended our clinic. Seven autoantibodies were selected for cluster analysis: anti-DNA, anti-Sm, anti-RNP, anticardiolipin (aCL) immunoglobulin (Ig)G or IgM, lupus anticoagulant (LAC), anti-Ro, and anti-La. Two-step clustering and Kaplan-Meier survival analyses were used. Results. Five clusters were identified. A cluster consisted of patients with only anti-dsDNA antibodies, a cluster of anti-Sm and anti-RNP, a cluster of aCL IgG/M and LAC, and a cluster of anti-Ro and anti-La antibodies. Analysis revealed 1 more cluster that consisted of patients who did not belong to any of the clusters formed by antibodies chosen for cluster analysis. Sm/RNP cluster had significantly higher incidence of pulmonary hypertension and Raynaud phenomenon. DsDNA cluster had the highest incidence of renal involvement. In the aCL/LAC cluster, there were significantly more patients with neuropsychiatric involvement, antiphospholipid syndrome, autoimmune hemolytic anemia, and thrombocytopenia. According to the Systemic Lupus International Collaborating Clinics damage index, the highest frequency of damage was in the aCL/LAC cluster. Comparison of 10 and 20 years survival showed reduced survival in the aCL/LAC cluster. Conclusion. This study supports the existence of autoantibody clusters with distinct clinical features in SLE and shows that forming clinical subsets according to autoantibody clusters may be useful in predicting the outcome of the disease. Autoantibody clusters in SLE may exhibit differences according to the clinical setting or population.

Metabolic syndrome is not only a risk factor for cardiovascular diseases in systemic lupus erythematosus but is also associated with cumulative organ damage: a cross-sectional analysis of 311 patients.

Background/Purpose Patients with systemic lupus erythematosus (SLE) have increased rates of cardiovascular disease (CVD) that are one of the major causes of mortality. The aim of this study was to determine the frequencies of metabolic syndrome (MetS) and CVD in SLE patients and investigate the link between these and clinical features of SLE. Methods A total of 311 SLE patients were consecutively assessed for cumulative organ damage (SDI/SLICC scores), history of CVD and MetS as defined by the National Cholesterol Educational Program Adult Treatment Panel III (NCEP ATP III). Clinical data of SLE patients were collected from the records. Results The mean age of the patients was 40.2 ± 13.4 years and 89% were female. The frequencies of CVD and MetS were 15.2% and 19%, respectively. In this SLE cohort increased age, cumulative damage, disease duration and CVD were associated with MetS. CVD was associated with disease duration, cumulative damage, pericarditis, hematologic involvement, lymphopenia, thrombocytopenia, neurological involvement and antiphospholipid antibody (aPL) positivity. Hydroxychloroquine (HCQ) use was found as a protective factor for CVD. Conclusion In SLE patients, MetS was associated with CVD and both increased with disease duration. Patients who developed MetS and/or CVD had increased cumulative organ damage. Certain clinical features of SLE and the presence of aPL were also associated with CVD. There was a significant protective effect of HCQ from CVD. The prevention of MetS and long-term use of HCQ may be beneficial in improving the prognosis of SLE.

Pulmonary arterial hypertension related to connective tissue diseases

Pulmonary arterial hypertension (PAH) is an important complication of connective tissue diseases (CTD) and especially seen in systemic sclerosis, systemic lupus erythematosis (SLE), and mixed connective tissue disease (MCTD). In systemic sclerosis, PAH is isolated or accompanied by interstitial lung disease and currently, a major cause of mortality. It has been shown to be developed in approximately 10% of cases and annual screening with echocardiography has been recommended. Right heart catheterization is required for definite diagnosis. Limited skin involvement, late onset, Raynauds phenomenon, digital ulcers, telangiectasias, diminished nail fold capillaries, anti-U3RNP and anticentromere antibodies are known as risk factors for PAH development in systemic sclerosis. Following diffusion lung capacity for carbon monoxide (DLCO) and pro-brain natriuretic peptide (pro-BNP) levels can be helpful for evaluating PAH development. PAH in SLE linked to antiphospholipid antibodies and Raynauds phenomenon in some studies. MCTD is an overlap syndrome with features of systemic sclerosis, SLE, polymyositis and positive anti-U1RNP antibodies. PAH develops in 9-27% of the patients and the leading cause of mortality in patients with MCTD. Endothelin receptor antagonists, prostacyclin analogs and phosphodiesterase 5 inhibitors are being used in patients with systemic sclerosis. In SLE/MCTD patients with early diagnosis immunosuppressive treatments may be effective.

Short report: correlates of functional disability with disease activity in elderly patients with rheumatoid arthritis

Abstract Rheumatoid arthritis (RA) prevalence increases with age and old people are special patient population. The recognition of functional disability related to RA could be challenging in elderly patients because aging itself and potential co-morbid disease may also cause functional disability. In this study, we aimed to look at the correlation between disease activity and functional disability in elderly RA patients. Elderly RA patients, ≥65 years old at their routine visits were included in the study. The composite ‘disease activity score’ in 28 joints (DAS-28) was used to determine disease activity groups. Health assessment questionnaire (HAQ) scores were calculated to describe the functional disability and compared across the disease activity groups. Two hundred and fifty-eight RA patients with the mean age of 71 ± 5 (65–90) and a total disease duration of 8.4 ± 8.5 (.5–50) years were recruited. The proportion of patients with high and moderate disease activity was 70%. HAQ scores were significantly correlated with disease activity (p < .05). Functional disability estimated by HAQ was correlated with disease activity in elderly patients with RA

Increased serum leptin levels are associated with metabolic syndrome and carotid intima media thickness in premenopausal systemic lupus erythematosus patients without clinical atherosclerotic vascular events

Aim To assess subclinical atherosclerosis and the role of inflammatory mediators, vascular endothelial cell activation markers and adipocytokines in systemic lupus erythematosus (SLE) in the presence or absence of metabolic syndrome (MetS). Methods We studied 66 premenopausal female SLE patients (20 with MetS) and 28 female healthy controls (HCs) without history of cardiovascular disease (CVD). Subclinical atherosclerosis was screened by measuring carotid intima media thickness (CIMT). Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor α (TNFα), interleukin 6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin, leptin and visfatin were measured. Results The mean age of MetS+SLE, MetS- and HC were 38.3 ± 6.7, 32.7 ± 9.3 and 29.9 ± 5.6 years, respectively. The mean disease duration, SLICC (Systemic Lupus International Collaborating Clinics damage index) and Systemic Lupus Erythematosus Disease Activity Index scores were 74.8 ± 54.9 months, 0.16 ± 0.48 and 1.18 ± 1.5, respectively, and were similar between MetS+and MetS- SLE patients. CIMT values were higher in both MetS+ and MetS- SLE patients than HCs (p < 0.001). sICAM-1 and erythrocyte sedimentation rate levels were higher in both MetS+ and MetS- SLE patients than HCs (p < 0.001; p = 0.002, p = 0.001). The SLE MetS+ group had higher CIMT values than SLE MetS- (right: p = 0.003; left: p = 0.025). Leptin levels and homeostatic model assessment (HOMA) scores were significantly higher in SLE MetS+ than SLE MetS- (p = 0.018; p = 0.04). Leptin and CRP levels and body mass index, SLICC and HOMA scores were correlated with CIMT values (right: p = 0.03, p < 0.001, p < 0.001, p = 0.026 and p < 0.001, and left: p = 0.028, p = 0.03, p = 0.003, p = 0.002 and p = 0.025). Conclusions In premenopausal women with SLE without a history of CVD, CIMT values were increased and related to MetS. Leptin was increased in patients with MetS and correlated with CIMT values.

AB0350 Functional disability measured by health assessment questionnaire (HAQ) correlates with disease activity in elderly rheumatoid arthritis patients

Background Rheumatoid arthritis (RA)s prevalence increases with age and the recognition of functional disability related to RA could be challenging in elderly patients (1). Objectives In this study, we aimed to look at the correlation between disease activity and the functional disability by using HAQ score in elderly RA patients. Methods Elderly RA patients, ≥65 years old at their routine visits were included to the study. The composite “disease activity score” in 28 joints (DAS-28) and “Physician Global Assessment” (PhGA) were used to determine disease activity. Health assessment questionnaire (HAQ) scores were calculated to describe the functional disability and compared across the disease activity groups according to DAS-28. Results Two hundred and fifty eight RA patients with the mean age of 71±5 (65–90) were included. Seropositivity rate was 71% and 47% of the patients had erosive disease. Joint deformity was seen in 72 (28%) of patients and 28 (11%) patients had undergone total arthroplasty. Lung involvement (8.5%) and Sjogrens syndrome (7.4%) were found as the most frequent extra-articular manifestations. Hypertension (66%) and osteoporosis (36%) were the common co-morbidities. The proportion of patients with high and moderate disease activity was found as 70%. HAQ and PhGA scores were significantly correlated with the disease activity (Figure).Figure 1. HAQ and PhGA distribution in disease activity subgroups. Both of them were found correlated with disease activity (p: 0.000). Conclusions We provided a novel data concerning the usefulness of HAQ for prediction of disease activity in RA patients who are elderly as well. In the future, our report will be supported by the studies which suggest that HAQ score improve with effective treatment in elderly RA patients. References Uhlig T, Loge JH, Kristiansen IS, Kvien TK. Quantification of reduced health-related quality of life in patients with rheumatoid arthritis compared to the general population. J Rheumatol 2007;34: 1241–1247. Disclosure of Interest None declared

AB0286 Clinical Features and Therapeutic Considerations in Elderly Patients with Rheumatoid Arthritis; A Cross-Sectional Study

Background Rheumatoid arthritis (RA)s prevalence increases with age. The average life expectancy is getting longer and global population is becoming older. Physicians will be challenged with the recognition and treatment of RA patients who may have different physical conditions, comorbid diseases and using multi-drugs. Objectives The aim of this study was to evaluate the clinical characteristics and treatment modalities in elderly RA patients. Methods We assessed elderly RA patients (≥65 years) diagnosed according to 2010 American College of Rheumatology (ACR) criteria. Clinical and laborotary findings, treatment durations, dose of drugs and treatment related adverse effects were recorded into a pre-defined protocol. “Disease Activity Score” (DAS-28), “Physician Global Assessment” (PGA) and “Health Assessment Questionnaire” (HAQ) scores were used as composite indices for RA activity evaluation. Results Seventy-four RA patients [54 patients (73%) were female] with a mean age of 71±5 (65–86) years were included into the study,. The mean total disease duration of these patients was 97±104 (9–600) months. Disease onset was in the elderly period for 40 (55%) patients. Small joints of hands were the most frequently involved joints (95%). Seropositivity rate was 66% and 56% of the patients had erosive disease. DAS-28 and HAQ scores were correlated with PGA scores (p:0,001). The proportion of patients with high and moderate disease activity was found as 79% according to DAS-28 scores. There was no association between age and antibody titers or activity indices. Non-steroidal antiinflammatory drugs (NSAIDs) were part of the treatment in 53 patients (71%) and no severe side effects associated with NSAIDs were observed. The mean cumulative prednisolone dose was 7617±10602 mg. Hypertension and osteoporosis were the most frequent comorbidities (64% and 48%, respectively). The most commonly used disease modifying antirheumatic drug (DMARD) was methotrexate (76%) and the rate of compliance was found high for all drugs except sulfasalazine (Table 1). While 60% of all patients were treated with DMARD monotherapy, combination DMARD therapy were used in 37% of patients. The rate of biologic theraphy was found as 12% (9 patients) in all study population.Table 1. The anti-rheumatic treatments in elderly RA patients Drugs n (%) Mean ages Starting in ≥65 age Mean dose Treatment duration* Maintanence of the theraphy n (%) n (%) Methotrexate 58 (79) 70,9±5 42 (73) 11,2±4,7mg/w 38,1±51 41 (72) Hydroxychloroquine 35 (48) 71,9±5 25 (74) 206±37mg/d 30,8±37 31 (91) Leflunomide 28 (39) 72±6 20 (74) 18,4±3,5mg/d 29,5±29 20 (77) Sulfasalazine 13 (18) 71,3±5 7 (53) 1,8±0,3g/d 47,1±69,2 5 (45) Rituximab 5 (6,7) 72,6±6 5 (100) 1000mgx2/2w 6,2±3 5 (100) Etanercept 2 (2,7) 65,5 21 (50) 50mg/w 13,5±14,8 1 (50) Abatacept 1 (1,3) 66 1 (100) 125mg/w 6 1 (100) Adalimumab 1 (1,3) 71 1 (100) 40mg/d 24 1 (100) *The mean treatment duration as months. Conclusions In this preliminary data from our ongoing study, elderly RA patients had remarkable compliance with NSAIDs and DMARDs. Although patients treated with biologic agents constituted a small group, no serious side effect that required cessation of the treatment was observed. By the increasing numbers of elderly RA patients in our cohort, we expect to obtain more powerful data on compliance and safety issues of the treatment and particularly biologic agents. Disclosure of Interest None declared

AB0510 The relationship between nailfold capillaroscopic assessment and telangiectasia score with severity of peripheral vascular involvement in systemic sclerosis

Objectives To determine the association of nailfold videocapillaroscopy(NVC)findings and telangiectasia score with DU history and severity of peripheral vascular involvement(PVI) in Systemic Sclerosis(SSc). Methods Fifty-nine SSc patients fulfilling Leroy and Medsger criteria were evaluated including Telangiectasia Score(TS)(Shah AA et al. J Rheumatol 2010), Modifiye Rodnan Skin Score(MRSS), Valentine Activity Scale(VAS) and Medsger Severity Scale(SS). Qualitative(early, active and late patterns) and semiquantitative assessments [capillary number(CN), irregularly enlarged capillaries(IEC), giant capillaries(GC), capillary ramifications(CR), microhaemorrhages(H), capillary array disorganisation(CAD) and microangiopathy evolution score(MES)]. was performed by NVC(Sulli et al. Ann Rheum Dis 2008) Results The mean age of patients was 45.6 and 91,5% were females. The mean duration of Raynaud’s(RS), non-Raynaud symptoms(NRS), skin involvement(SI)(year) were 6.1±6.5, 3.1±2.0, 3.0±2.0 respectively. Of the patients 20(34%) were diffuse cutaneous,35(59%) were limited and 4(7%) were sine-scleroderma;13(22%) were anti-centromere(+) and 29(49%) were anti-Scl70(+). DU history (DU+) was present in 27(46%) and telangiectases were present in 34(58%). When we compare DU- and DU + groups, the mean score of CN was 1.4±0.7 vs 2.0±0.5*(p<0.001), IEC was 1.4±0.7 vs 1.8±0.6**(p<0.05), MES was 1.8±1.0 vs 2.5±1.5**(p<0.05); early pattern was in 9 vs 1, active pattern was in 16 vs 14, late pattern was in 7 vs 12 patients. Current PVI grouped as Not Severe(SS;0-1)(n=43) or Severe(SS;2-4)(n=16). The frequency of severe PVI was 22% in females(12/54) and 80% in males(4/5). The mean values of TS, MRSS, VAS, SS were similar between groups. When we compare Not Severe and Severe groups, the mean score of CN was 1.5±0.7 vs 2.1±0.4*(p<0.001), MES was 1.8±1.1 vs 2.8±1.6** (p<0.05); early pattern was in 10 vs 0, active pattern was in 21 vs 9, late pattern was in 12 vs 7 patients. Conclusions DU history and severe PVI in SSc was associated with capillary loss and microangiopathy. ‘Early’ NVC pattern was very rare in patients with DU history and was not found in severe PVI. Severe PVI in males was more frequent than females. Telangiectasia scores were not found to be related to PVI. NVC may be a helpful method in the assessment of SSc patients for PVI prognosis, warranting prospective studies. Disclosure of Interest None Declared

SAT0164 Favourable Pregnancy Outcome in Takayasu’S Arteritis: A Single Center Experience

Background Takayasu’s arteritis (TA) is a large vessel vasculitis of the young women in their reproductive age. It’s been previously reported as having conflicting results on the pregnancy outcome in TA. Objectives Herein, we reported the pregnancy outcome and the effect of the pregnancy on the disease course in a well established TA cohort. Methods TA patients diagnosed by ACR criteria and had the history of pregnancy were included into the study. Clinical and laboratory findings including serum ESR and CRP levels were evaluated both retrospectively and prospectively. Pregnancy and newborn outcome consists of the history of abortus, delivery mode, prematurity, intrauterin growth retardation, preeclampsia and eclampsia that were obtained from medical records. Data were noted into a predefined protocol. Disease activity and damage evaluated by Kerr criteria and VDI and concomittant immunosuppressives were recorded within the 3rd trimester and 6 months of pre and postpartum period in a subgroup prospectively followed-up. Pre-diagnosis (pre-d) and post-diagnosis (post-d) pregnancies were compared according to the maternal and fetal outcome. Results Eighty-two pregnancies in 34 patients were assessed in TA cohort of 103 patients. Only 10% of all pregnancies were planned. Mean (median) age of 34 patients at pregnancy period were 24,5±6,6 (22). Subclavian (85%), carotis (44%) and pulmonary arteries (26%) were the most frequently involved vessels. Hypertension (47%), pulselessness (%34), mild pulmonary hypertension (18%) related to valvular disease (26%) were the prominent clinical features. Comparison of fetomaternal prognosis between the pre-d (63 in 24 TA) and post-d (19 in 15 TA) pregnancies demonstrated that hypertension (3% vs 16%), preeclampsia (0% vs 10%), prematurity (2% vs 10%) and Cesarean section (CS) (9% vs 37%) were significantly high in post-d pregnancies. Eight patients (of 4 newly diagnosed) prospectively followed-up during their pregnancies. Glucocorticoid (GC) (4 pts) and azathioprin (2 pts) were maintained after taking the patients’ consents. Four patients had flare during the 3rd trimester. Two of 4 patients had taken 10 mg/d GC and other 2 patients denied to be treated. The patient had renal artery involvement complicated with preeclampsia and the other experienced accelerated hypertension. Five TA patients underwent Ceaserean section mainly because of the probable risk of cerebral hypoperfusion during the delivery. One TA patient who was exposed to infliximab during the conception, has since been followed-up succesfully at the 3rd trimester under the low dose of GC. There were no obvious fetomaternal abnormality in TA cohort. No flare was observed during the 6th month of postpartum period. VDI scores did not increase in all patients. Conclusions Majority of the pregnancies were found as successfull in a well established TA cohort. Higher rates of preeclampsia, prematurity and CS in post-d pregnancies were attributed to the exposure of GC treatment and physicians’ bias for delivery route. CS and prematurity were found as similar with our healthy population rates. Flares did not cause damage accrual in a short postpartum follow-up period. Flare has to be differentiated from the aberrant physiological changes and acute phase increase during the pregnancy. Close monitorization of arterial tension could be helpful for maintaining succesful pregnancy Disclosure of Interest None Declared