Omer Gendelman

High proportions of dementia among SLE patients: A big data analysis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a wide range of systems including the peripheral and central nervous system. Cognitive impairment leading to dementia is one of the harmful central nervous system afflictions of SLE. The aim of this study was to investigate the association of SLE with dementia.

The association between systemic lupus erythematosus and bipolar disorder – a big data analysis

BACKGROUND Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease that has a wide variety of physical manifestations, including neuropsychiatric features. Bipolar disorder (BD) is a chronic, episodic illness, that may present as depression or as mania. The objective of this study was to investigate the association between SLE and BD using big data analysis methods. METHODS Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of BD in a cross-sectional study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis, adjusting for confounders. The study was performed utilizing the chronic disease registry of Clalit Health Services medical database. RESULTS The study included 5018 SLE patients and 25,090 matched controls. BD was found in a higher prevalence among SLE patients compared to controls (0.62% vs. 0.26%, respectively, P<0.001). BD patients had a greater prevalence of smokers compared to non-BD patients (62.5% vs 23.5%, respectively, P<0.001). In a multivariate analysis, smoking and SLE were both found to be significantly associated with BD. CONCLUSIONS SLE was found to be independently associated with BD. These findings may imply that an autoimmune process affecting the central nervous system among SLE patients facilitates the expression of concomitant BD.

Rituximab-induced remission in a woman with coexisting rheumatoid arthritis and nephrotic syndrome

We describe a patient with rheumatoid arthritis who presented with nephrotic syndrome which was not related neither to drug therapy nor to amyloidosis. Renal biopsy revealed membranous glomerulonephritis. The patient was treated with three cycles of rituximab with complete resolution of the clinical and laboratory evidence of nephrosis. The following report discusses this unusual presentation and clinical response.

Ischemic heart disease and ankylosing spondylitis—assessing the role of inflammation

To assess the association of ankylosing spondylitis (AS) and ischemic heart disease (IHD) compared to traditional cardiovascular (CV) risk factors. Primary care and hospital records of patients with AS were analyzed, using the largest health maintenance organization in Israel, the “Clalit” Health Services data. These patients were compared with age- and gender-matched controls regarding the proportion of IHD in a cross-sectional study. Parameters including socioeconomic status, body mass index (BMI), smoking habits, and coexistent medical conditions hypertension, hyperlipidemia, and diabetes mellitus (DM) - as well as the use of NSAIDs and anti-TNFs were also assessed. The study included 4076 AS patients compared to 20,290 age- and gender-matched controls without AS. The proportion of IHD was higher among AS patients as compared to controls (14.1 vs. 6.36%, respectively, p < 0.01) and patients treated with anti-TNFs had a lower risk for IHD compared to non-anti-TNF users. The proportion of hypertension, hyperlipidemia, DM, and smoking was also higher among AS patients. However, in multivariate analyses following adjustment to these risk factors, AS was not found to be associated with IHD nor anti-TNF therapy to be a protective factor. Patients with AS have more traditional CV risk factors, thus are in a higher risk for IHD. AS itself was not shown to be independently associated with IHD. These findings emphasize the multifactorial process leading to increased proportion of IHD among AS patients and the need for a stringent control of traditional risk factors in these patients.

Pericarditis among giant cell arteritis patients: From myth to reality

Giant cell arteritis (GCA) is an inflammatory disease of unknown etiology affecting adults age > 50 years. GCA (also known as temporal arteritis) is a vasculitis of large and medium‐size vessels that involves the extracranial branches of the carotid artery. Common manifestations include constitutional symptoms, headache, jaw claudication, scalp tenderness, and vision loss. Cardiac involvement in GCA is considered to be as low as 5%, and < 30 cases of pericarditis among GCA patients have been reported in the literature. The aim of this study was to evaluate the association between GCA and pericarditis by conducting a cross‐sectional study utilizing the database of the largest healthcare provider in Israel.

SAT0545 Giant cell arteritis and hematologic malignancies: a real-life experience

Background Giant cell arteritis (GCA), also known as temporal arteritis, is a vasculitis of large and medium-sized vessels, which commonly involves the extracranial branches of the carotid artery. There are conflicting evidence regarding the association between GCA and both solid and hematologic malignancies.1–4 Objectives To assess the coexistence rate of GCA and hematologic malignancies. Methods This cross-sectional study was performed utilising the database of Israel’s largest healthcare association, Clalit Health Services (CHS). All patients with previously documented diagnosis of GCA were included, as well as age-and sex matched controls without GCA. The proportions of Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma and multiple myeloma were compared between patients and controls. Univariate analysis was compared using chi-square test for categorical variables and student’s t-test for continuous variables. A multivariable logistic regression model was built to assess the covariates associated with each Non-Hodgkin’s lymphoma, the hematologic malignancy with the highest number of patients. Results The study included 5,663 GCA patients and 28 308 controls with a mean age of 71 and 68.3, respectively. Both groups consisted of 69.8% females. Multiple myeloma was observed in 27 GCA patients (0.48%) and 53 controls (0.19%), crude OR=2.56 p<0.001. Hodgkin’s lymphoma was observed in 19 GCA patients (0.34%) and 41 controls (0.14%), crude OR=2.33 p=0.004. Non-Hodgkin’s lymphoma was observed in 64 GCA patients (1.13%) and 164 controls (0.58%), crude OR=1.96 p<0.001. Multivariable logistic regression model adjusting for age and gender found GCA as independently associated with Non-Hodgkin’s lymphoma (adjusted OR 1.96, p<0.001). Characteristic No GCA n=28 308 GCA n=5663 OR p.ratio Age 68.3±27.4 71.0±15.6 1.00 [1.00;1.00] <0.001 Gender: Female 19 767 (69.8%) 3954 (69.8%) 1.00 [0.94;1.06] 0.991 BMI 28.2±5.91 28.1±5.60 1.00 [0.99;1.00] 0.081 Socioeconomic status: Low 5443 (36.8%) 1970 (34.9%) Ref. Ref. Medium 6241 (42.2%) 2339 (41.4%) 1.04 [0.97;1.11] 0.330 High 3093 (20.9%) 1336 (23.7%) 1.19 [1.10;1.30] <0.001 Multiple Myeloma 53 (0.19%) 27 (0.48%) 2.56 [1.59;4.04] <0.001 Hodgkin’s Lymphoma 41 (0.14%) 19 (0.34%) 2.33 [1.32;3.97] 0.004 Non-Hodgkin’s Lymphoma 164 (0.58%) 64 (1.13%) 1.96 [1.46;2.61] <0.001 Conclusions GCA patients have higher rate of hematologic malignancies compared to controls. The association with Non-Hodgkin’s lymphoma is the most prominent, and proper screening methods should be applied for early detection and treatment. References [1] Askling J. Do steroids increase lymphoma risk? A case-control study of lymphoma risk in polymyalgia rheumatica/giant cell arteritis. Ann Rheum Dis64:1765–1768. doi:10.1136/ard.2005.036459 [2] Liozon E, Loustaud V, Fauchais A-L, et al. Concurrent temporal (giant cell) arteritis and malignancy: report of 20 patients with review of the literature. J Rheumatol2006;33:1606–1614. [3] Kermani TA, Schäfer VS, Crowson CS, et al. Malignancy risk in patients with giant cell arteritis: A population-based cohort study. Arthritis Care Res NA-NA. doi:10.1002/acr.20062 [4] Solans-Laque R, Bosch-Gil JA, Pérez-Bocanegra C, et al. Paraneoplastic vasculitis in patients with solid tumors: report of 15 cases. J Rheumatol35:294–304. Disclosure of Interest None declared

OP0087 Increased risk of ischaemic heart disease and mortality among fmf patients – perspective from a big database

Background Familial Mediterranean fever (FMF) is a systemic autoinflammatory monogenic disease. It has been previously reported that FMF patients are prone to develop ischaemic heart disease (IHD),1 2 mostly due to increased inflammatory activity and endothelial dysfunction.3 4 However, large-scale information regarding the extent and prognosis of IHD among FMF patients is lacking. Objectives To check whether an association exists between FMF and IHD, and to assess the long-term prognostic significance of IHD among FMF patients using a big data registry with a 15 year follow-up period. Methods Utilising the medical records of Clalit Health Services, the largest HMO in Israel, we extracted a cohort of FMF patients along with their age-and-sex matched controls. Dates of registration in the medical records of FMF, IHD and death, as well as anthropometric information and medical comorbidities were extracted from the database. To compare the distribution of variables across the cohort strata, univariate analysis was performed using Chi-square and student t-test. Multivariate analysis using a logistic regression model was used to find variables associated with IHD. Survival analysis using Cox proportional hazards method and a log-rank test was performed to find variables associated with increased risk of all-cause mortality. Results The cohort included 7,670 FMF patients and 7670 age-and-sex matched controls. The mean age of both groups was 39.1, and both consisted 50.1% females. IHD was observed among 491 FMF patients (6.4%) vs 375 controls (4.89%), p<0.001. In multivariate logistic regression, FMF was found to be independently associated with a diagnosis of IHD (OR 1.44, 95% CI: 1.21 to 1.72). After over 15 years of follow-up, 345 (4.5%) of FMF patients had died, compared to 271 (3.53%) of the controls (p<0.001). In multivariate survival analysis, both FMF and IHD were found to be significantly associated with increased risk to all-cause mortality (HR 1.29, 95% CI: 1.10 to 1.53 and HR 1.57, 95% CI: 1.29 to 1.9, respectively). Conclusions IHD is associated with worse prognosis among FMF patients compared to controls. Proper screening methods are recommended to assess whether early identification and treatment may improve life expectancy. References [1] Langevitz P, Livneh A, Neumann L, et al. Prevalence of ischemic heart disease in patients with familial Mediterranean fever. Isr Med Assoc J IMAJ2001;3:9–12. [2] Twig G, Livneh A, Vivante A, et al. Cardiovascular and metabolic risk factors in inherited autoinflammation. J Clin Endocrinol Metab2014;99:E2123–E2128. doi:10.1210/jc.2014-2096 [3] Akdogan A, Calguneri M, Yavuz B, et al. Are Familial Mediterranean Fever (FMF) patients at increased risk for atherosclerosis? Impaired endothelial function and increased intima media thickness are found in FMF. J Am Coll Cardiol2006;48:2351–2353. doi:10.1016/j.jacc.2006.09.013 [4] Sari I, Karaoglu O, Can G, et al. Early ultrasonographic markers of atherosclerosis in patients with familial Mediterranean fever. Clin Rheumatol2007;26:1467–1473. doi:10.1007/s10067-006-0529-2 Disclosure of Interest None declared

THU0248 The association between systemic lupus erythematosus to bipolar disorder – a real-life study

Background Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune disease that has a wide variety of physical manifestations, including neuropsychiatric features. Bipolar Disorder (BD) is a chronic, phasic affective disorder that may present as depression or as mania. Neuropsychiatric symptoms in SLE develop in 20%>70% of SLE patients during the course of the disease and in half of these patients they precede the diagnosis of SLE1–4. In half of the patients, neuropsychiatric manifestations occur prior to the diagnosis of SLE5. Objectives The objective of this study was to investigate the association between SLE and Bipolar Disorder (BD) using big data analysis methods. Methods Patients with SLE were compared with age- and sex-matched controls regarding the proportion of BD in a cross-sectional study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis, adjusting for confounders. The study was performed utilizing the chronic disease registry of Clalit Health Services medical database. Results The study included 5,018 SLE patients and 25,090 matched controls. BD was found in a higher proportion among SLE patients compared to controls (0.62% vs. 0.26%, respectively, p<0.001). BD patients had a greater proportion of smokers compared to non-BD patients (62.5% vs 23.5%, respectively, p<0.001). In a multivariate analysis, smoking and SLE were both found to be significantly associated with BD. Multivariate logistic regression model of covariates associated with Bipolar disorder OR CI p Age 1.01 1.00, 1.02 0.137 Gender: Female 1.63 0.96, 2.97 0.087 SES:  Medium vs. Low 1.06 0.66, 1.69 0.816  High vs. Low 1.17 0.67, 1.98 0.575 Smoking 4.80 3.16, 7.39 <0.001 SLE 1.74 1.11, 2.66 0.012 SES: Socioeconomic status, SLE: Systemic lupus erythematosus. Conclusions SLE was found to be independently associated with BD. These findings may imply that an autoimmune process affecting the central nervous system among lupus patients facilitates the expression of concomitant BD. References Kivity S, Shoenfeld Y. Association between autoantibodies and neuropsychiatric manifestations of autoimmune disease: comment on the article by Lauvsnes et al. Arthritis Rheumatol 2015; 67(6):1683. Meszaros ZS, Perl A, Faraone SV. Psychiatric symptoms in systemic lupus erythematosus: a systematic review. J Clin Psychiatry 2012; 73(7):993–1001. Unterman A, Nolte JE, Boaz M, Abady M, Shoenfeld Y, Zandman-Goddard G. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum 2011; 41(1):1–11. Zandman-Goddard G, Chapman J, Shoenfeld Y. Autoantibodies involved in neuropsychiatric SLE and antiphospholipid syndrome. Semin Arthritis Rheum 2007; 36(5):297–315. Kivity S, Agmon-Levin N, Zandman-Goddard G, Chapman J, Shoenfeld Y. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med 2015; 13:43. Disclosure of Interest None declared

OP0078 The long term prognostic significance of pulmonary hypertension in sarcoidosis - a big data analysis

Background Sarcoidosis is a multisystem, chronic, progressive, granulomatous disease. Sarcoidosis-associated pulmonary hypertension is well described, but not common complication of sarcoidosis1. In small scale studies, it has been previously described as a manifestation of advanced disease and was found to be associated with increased morbidity and mortality2. Previous studies have shown that treatment may be safe and improve pulmonary hemodynamics in sarcoidosis-associated pulmonary hypertension3,4. However, big data analyses regarding the exact magnitude and prognosis of sarcoidosis-associated pulmonary hypertension are lacking. Objectives To assess the long-term prognostic significance of sarcoidosis-associated pulmonary hypertension using a big data registry with a 15-year follow-up period. Methods Utilizing the medical records of Clalit Health Services, the largest HMO in Israel, we extracted a cohort consisted of sarcoidosis patients along with their age-and-sex matched controls. Dates of registration in the medical records of sarcoidosis, pulmonary hypertension and death, as well as anthropometric information and medical comorbidities were extracted from the database. To compare the distribution of variables across the cohort strata, univariate analysis was performed using Chi-square and student t-test. Multivariate analysis using a logistic regression model was used to find variables associated with pulmonary hypertension. Survival analysis using cox proportional hazards method and log-rank test was performed to find variables associated with increased risk of all-cause mortality. Results The cohort included 3,993 sarcoidosis patients and 19,856 age-and-sex matched controls. The mean age of both groups was 56, and both consisted about 63% females. Pulmonary hypertension was observed among 269 sarcoidosis patients (6.74%) vs. 400 controls (2.01%), p<0.001. In multivariate analysis, sarcoidosis was found to be independently associated with diagnosis of pulmonary hypertension (OR 3.09, 95% CI 2.6–3.67). After more than 15 years of follow-up, 710 (17.8%) of the sarcoidosis patients had died, compared to 2121 (10.7%) of the controls (p<0.001). In multivariate survival analysis, both sarcoidosis and pulmonary hypertension were found to be significantly associated with increased risk to all-cause mortality (HR 1.83, 95% CI 1.66–2.02 and HR 2.32, 95% CI 2.05–2.63, respectively). Conclusions Sarcoidosis-associated pulmonary hypertension is associated with poor prognosis. Proper screening methods are recommended to assess whether early identification and treatment may improve life expectancy. References Baughman, R. P., Culver, D. A. & Judson, M. A. A Concise Review of Pulmonary Sarcoidosis. Am. J. Respir. Crit. Care Med. 183, 573–581 (2011). Baughman, R. P., Engel, P. J., Taylor, L. & Lower, E. E. Survival in Sarcoidosis-Associated Pulmonary Hypertension. Chest 138, 1078–1085 (2010). Baughman, R. P. et al. Bosentan for Sarcoidosis-Associated Pulmonary Hypertension. Chest 145, 810–817 (2014). Keir, G. J. et al. Treatment of sarcoidosis-associated pulmonary hypertension: A single centre retrospective experience using targeted therapies. Sarcoidosis Vasc. Diffuse Lung Dis. 31, 82–90 (2014). Disclosure of Interest None declared