Esther Uriarte

PERMANENT VISUAL LOSS AND CEREBROVASCULAR ACCIDENTS IN GIANT CELL ARTERITIS Predictors and Response to Treatment

OBJECTIVE To assess the features and therapeutic response of visual manifestations and cerebrovascular accidents (CVA) in giant cell (temporal) arteritis (GCA) and to identify the predictors for permanent visual loss (VL) and CVA in GCA. METHODS Two hundred thirty-nine patients with biopsy-proven GCA were included in a retrospective multicenter study. Data on demographic, clinical, and laboratory features were collected. The predictors were identified by a forward stepwise nonconditional logistic regression analysis. RESULTS Visual involvement was observed in 69 patients, and 34 had permanent VL. The diagnostic delay since the onset of visual symptoms was longer in the 11 patients with bilateral VL. The interval to involvement of the second eye was 5 days. The predictors of permanent VL were transient VL, jaw claudication, normal levels of liver enzymes, and absence of constitutional syndrome. Partial improvement of visual acuity was observed in 8 patients. After adjustment for the treatment regimen (intravenous pulse methylprednisolone versus oral prednisone), early treatment (within the first day of VL) was the only predictor of improvement. CVA, observed in 8 patients, involved the vertebral-basilar territory in 4. CVA was more frequent in patients with visual symptoms, appearing shortly after VL (median 7 days) and despite appropriate therapy. Predictors of CVA were permanent VL and jaw claudication. CONCLUSION In GCA, the risk of permanent VL is increased in patients with transient VL and/or jaw claudication, and decreased in those with elevated liver enzyme levels and/or constitutional syndrome. Partial therapeutic success is more probable if treatment is started within the first day of VL. CVA is more likely in patients with permanent VL and/or jaw claudication, often developing despite appropriate corticosteroid therapy.

Comprehensive Description of Clinical Characteristics of a Large Systemic Lupus Erythematosus Cohort from the Spanish Rheumatology Society Lupus Registry (RELESSER) With Emphasis on Complete Versus Incomplete Lupus Differences

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries.RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions.A total of 4.024 SLE patients (91% with ≥4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis—adjusted by gender, age at diagnosis, and disease duration—revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08–1.20 (P < 0.001); 1.29; 95% CI: 1.15–1.44 (P < 0.001); and 2.10; 95% CI: 1.83–2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0–4)], damage [median SLICC/ACR/DI: 1 (IQ: 0–2)], and severity [median KATZ index: 2 (IQ: 1–3)] scores were low, 1 of every 4 deaths was due to SLE activity.RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population.

Characterization of Patients With Lupus Nephritis Included in a Large Cohort From the Spanish Society of Rheumatology Registry of Patients With Systemic Lupus Erythematosus (RELESSER).

AbstractThe aim of the study was to profile those patients included in the RELESSER registry with histologically proven renal involvement in order to better understand the current state of lupus nephritis (LN) in Spain.RELESSER-TRANS is a multicenter cross-sectional registry with an analytical component. Information was collected from the medical records of patients with systemic lupus erythematosus who were followed at participating rheumatology units. A total of 359 variables including demographic data, clinical manifestations, disease activity, severity, comorbidities, LN outcome, treatments, and mortality were recorded. Only patients with a histological confirmation of LN were included. We performed a descriptive analysis, chi-square or Students t tests according to the type of variable and its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression.LN was histologically confirmed in 1092/3575 patients (30.5%). Most patients were female (85.7%), Caucasian (90.2%), and the mean age at LN diagnosis was 28.4 ± 12.7 years. The risk for LN development was higher in men (M/F:47.85/30.91%, P < 0.001), in younger individuals (P < 0.001), and in Hispanics (P = 0.03). Complete response to treatment was achieved in 68.3% of patients; 10.35% developed ESRD, which required a kidney transplant in 45% of such cases. The older the patient, the greater was the likelihood of complete response (P < 0.001). Recurrences were associated with persistent lupus activity at the time of the last visit (P < 0.001) and with ESRD (P < 0.001). Thrombotic microangiopathy was a risk factor for ESRD (P = 0.04), as for the necessity of dialysis (P = 0.01) or renal transplantation (P = 0.03). LN itself was a poor prognostic risk factor of mortality (OR 2.4 [1.81–3.22], P < 0.001). Patients receiving antimalarials had a significantly lower risk of developing LN (P < 0.001) and ESRD (P < 0.001), and responded better to specific treatments for LN (P = 0.014).More than two-thirds of the patients with LN from a wide European cohort achieved a complete response to treatment. The presence of positive anti-Sm antibodies was associated with a higher frequency of LN and a decreased rate of complete response to treatment. The use of antimalarials reduced both the risk of developing renal disease and its severity, and contributed to attaining a complete renal response.

Incidence, associated factors and clinical impact of severe infections in a large, multicentric cohort of patients with systemic lupus erythematosus

OBJECTIVES To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ≥1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (≥10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect.

Comorbidities in patients with Primary Sjögren's Syndrome and Systemic Lupus Erythematosus: A comparative registries‐based study

To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögrens syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on cardiovascular (CV) diseases.

Pure Membranous Lupus Nephritis: Description of a Cohort of 150 Patients and Review of the Literature

OBJECTIVES The course and long-term outcome of pure membranous lupus nephritis (MLN) are little understood. The aims of this study are to evaluate the clinical features, course, outcome and prognostic indicators in pure MLN and to determine the impact of ethnicity and the type of health insurance on the course and prognosis of pure MLN. METHODS We conducted a retrospective review of medical records of 150 patients with pure MLN from Spain and the USA. RESULTS Mean age was 34.2±12.5 and 80% were women. Sixty-eight percent of patients had nephrotic syndrome at diagnosis. The average serum creatinine was 0.98±0.78mg/dl. Six percent of patients died and 5.3% developed end-stage renal disease (ESRD). ESRD was predicted by male sex, hypertension, dyslipidemia, high basal 24h-proteinuria, high basal serum creatinine and a low basal creatinine clearance. Age, cardiac insufficiency, peripheral artheriopathy, hemodialysis and not having received mycophenolate mofetil or antimalarials for MLN predicted death. CONCLUSIONS Pure MLN frequently presents with nephrotic syndrome, high proteinuria and normal serum creatinine. Its prognosis is favourable in maintaining renal function although proteinuria usually persists over time. Baseline cardiovascular disease and not having a health insurance are related with poor prognosis.

AB0173 Mycobacterial infection in systemic lupus erythematosus: clinical significance and associated factors. data from the registry of patients with sle of the spanish society of rheumatology (RELESSER)

Objectives To study the prevalence of mycobacterial infection (MI), the associated factors and their clinical significance in patients included in a large SLE cohort. Methods Retrospective descriptive study of RELESSER patients with a history of MI and analysis of the factors associated with this infection. Results In RELESSER 3,658 patients with ≥4 ACR SLE criteria were included. 90% are women with a mean age of 32.9 years. 93% are Caucasians. The mean follow-up time (± SD) was 120.2 (± 87.6) months. 705 (19.3%) patients had ≥1 severe infection (defined as requiring admission); 1,227 severe infections occurred. MI were diagnosed in 42 patients (1.2% of all RELESSER patients, 3.4% of all severe infections), 85.7% women. The incidence rate of MI was 1 per 1,000 patients/year (95% CI:0.7–1.4). MI presentation was pulmonary in 18 (42.9%) patients and extrapulmonary in 24 (57.1%) patients [joints in 8 (19.0%) patients, soft tissue in 6 (14.3%) and other sites in 10 (23.8%)]. The extrapulmonary form was associated with immunosuppressants use: 84.6% of the 13 patients treated with immunosuppressive drugs versus 44.4% of the 27 patients without (p=0.01). We did not observe this association with the use of corticosteroids. To study the factors associated with MI, we performed a bivariate analysis including the variables associated with severe infection in RELESSER (age, sex, ethnicity, corticosteroids, immunosuppressants, antimalarials, previous admission by SLE activity, rituximab and anti-TNF use, Katz severity index, SDI index, SLEDAI index and Charlson comorbidity index). There is a statistically significant association with previous admission by SLE activity (RR:2.9, 95–95%:1.3–6.2, p=0.007), renal impairment (RR:2.0, CI 95%:1,1–3,7, p=0,04), the Katz score (RR:2.1, 95% CI:1.1- 4.0, p=0.04) and the Charlson index (RR: 2.5; 95% CI: 1.3–4.8, p=0.009). Damage (SDI>0) was closely associated with significance:RR: 2.0; 95% CI: 1.0–4.0, p=0.07. Iimmunosuppressants use was associated with an important increase in the risk of MI: RR:4.3; 95% CI:2.2–8.3, p=0.31. Two patients (4.8%) died (1 respiratory and 1 extrapulmonary). Mean survival after MI diagnosis in these cases was 21 days. Conclusions MI in RELESSER affects 1.15% of patients. Its incidence rate is 1 per 1,000 patients/year (95% CI:0.7–1.4). Extrapulmonary localization affects more than half of the patients and is associated with immunosuppressants use. Previous admission by SLE activity, renal involvement, SLE severity and increased number of comorbidities are factors associated with MI. Acknowledgements Work supported by Spanish Society of Rheumatology, FIS/ISCIII/FEDER (PI11/02857), BIOCAPS from the European Union 7th Framework Programme/REGPOT-2012–2013.1(316265), GSK, Roche, Novartis, UCB. Disclosure of Interest None declared

OP0042 Bacteremia in systemic lupus erythematosus patients from relesser registry: risk factors, clinical and microbiological characteristics and outcomes

Background According to RELESSER (Spanish Society of Rheumatology Lupus Registry) data, bacteremia is the main cause of death by infection in systemic lupus erythematosus (SLE). However, the available information about this severe infection in SLE patients remains scarce. Methods Retrospective, nested case-control study of SLE patients (ACR-97 criteria) with at least one bacteremic episode and random controls from RELESSER Registry. Descriptive, bivariate and multivariate analysis (logistic regression) Results 114 bacteremic episodes in 83 patients were recorded. Incidence rate: 2,7/ 1,000 patient-years (n total: 3658). At the time of the bacteremia: median age: 40.5 (8–90) years, 88.6% female, disease duration: 9.7 (IR16.7), median SELENA-SLEDAI: 4 (IR8), 66% with severe flare (SFI criteria), active nephritis: 16.7%, median SLICC/ACR DI: 3 (IR4), any comorbidity: 64% (McCabe-Jackson criteria: 28.1% rapidly or ultimately fatal), more frequently renal failure (15.8%) or diabetes (11.4%). SLE treatment at the time of bacteraemia: 88.6% corticosteroids (68,6%>10mg/day), 57% immunosuppressors (mycophenolate 17.5% and cyclophosphamide 12.3%), 27% antimalarials. 44.7% suffered invasive procedures, more frequently intravascular catheter (24.6%). The bacteremia was nosocomial in 35.1% and the source was more frequently urinary (27.2%). 64% developed systemic inflammatory response syndrome and 35% needed intensive care unit admission, with multiorganic failure in 22.8%. The most frequent microorganism was E.coli (29.8%) followed by Staphylococcus aureus (16.7%) (22% methicillin-resistant) and Salmonella spp. (10.5%). 16% of the gram-negative enteric bacilli were extended-spectrum b-lactamase positive. 17.5% were multidrug resistant. 68,4% started the antibiotherapy before blood culture results, resulting finally active in susceptibility testing in 56 cases (71.8%), indicating an appropriate empirical antibiotic therapy in 49%. The bacteremia-related mortality was 14%. The risk of death was higher in patients with severe sepsis (Pitt index >8) (OR: 13 (IC95%: 3.71–45.17). The bacteremia was recurrent in 26.3%. Associations with bacteremia in bivariate analysis (114 bacteremias vs 688 controls) are shown in Table 1. Antimalarials were protective. In the multivariate analysis (adjusted for disease duration), only elevated creatinine (OR 1.31 (95% CI 1.01–1.70), p=0.045), diabetes (OR 6.01 (95% CI 2.26–15.95), p=0.000), cancer (OR 5.32 (95% CI 2.23–12.70), p=0.000), immunosuppressors (OR 6.35 (95% CI 3.42–11.77), p=0.000), cyclophosphamide (OR 9.37 (95% CI 5.12–17.14), p=0.000) and SLICC/ACR DI (OR 1.65 (95% CI 1.31–2.09), p=0.000) remained statistically significant. Conclusions Bacteremia occurred mostly in active SLE, frequently in the context of a severe flare. Gram negative bacilli predominated, with high rate of multidrug resistance. The empiric treatment was inappropriate in a half of the cases. The recurrence and mortality were high. Immunosuppressors use, comorbidity and damage were all associated to bacteraemia. Disclosure of Interest None declared

SAT0391 Cumulative Incidence and Clinical Meaning of Severe Infection in a Large Spanish Cohort of Systemic Lupus Erythematosus

Background There are scanty data about infection in Systemic Lupus Erythematosus (SLE) patients from large multicenter cohorts. Objectives To describe the prevalence of severe infection (SInf), investigate associated factors and clinical meaning in a large SLE cohort from Spanish Rheumatology Society Lupus Registry (RELESSER). Methods Patients with Sinf were compared with patients without SInf in terms of severity, damage, comorbidities and demographic characteristics (bivariate analysis and Cox regression to survival until the first infection). Results A total of 3.658 SLE patients included, 90% female, median age 32.9 years (DQ 9.7), 93% Caucasian and 5% Hispanic (Amerindian,mestizo). Mean follow-up (months) was 120.2 (SD: ±87.6). A total of 705 (19.3%) of the patients suffered ≥1 SInf, with an overall of 1.227 SInf. The density of incidence was 29.2 (95%CI: 27.6 - 30.9) infections/ 1000 patients-year. The survival until second infection was lower than survival until first infection (log rank p<0.000). There was predominance of bacterial cause (51.9%), with a 30.4% of unknown cause, and the respiratory tract was the most frequent localization 35.5%. A total of 208 (5.7%) patients died during the follow-up period, 24.5% of them by infection. The predominant localization for the fatal infection was the circulatory stream (bacteraemia/sepsis) (42.0%). In the Cox proportional-hazards regression model age at diagnosis (HR 1.016; 95%CI: 1.009-1.023, p=0.0000) Hispanic ethnic (HR 2.151; 95%CI: 1.539-3.005 p=0.0000) corticosteroids (≥10 mg/day) (HR 1.271; 95%CI: 1.034-1.561, p=0.0224) immunosuppressors (HR 1.348; 95%CI: 1.079-1.684 p=0.0085), hospitalization by SLE (HR 2.567; 95%CI: 1.905-3.459, p=0.0000) renal involvement (HR 1.370; 95%CI: 1.130-1.660, p=0.0013), severity Katz index (SKI) (HR 1.160; 95%CI: 1.105-1.217, p=0.0000), damage index (SDI) (HR 1.069; 95%CI: 1.031-1.108, p=0.0003) and tobacco (HR: 1.332; 95%CI: 1.121-1.583, p=0.0011) were all associated with SInf. Time on antimalarials (months) proved to be protective (HR: 0.998; 95%CI: 0.997-0.999, p=0.0022) Conclusions SInf remains a frequent and potentially fatal complication of SLE and/or immunosuppressive therapies, and its a marker of more severe disease. Respiratory bacterial infections are the most common SInf in SLE, but bloodstream infections are the most common mortal ones. A previous infectious event seems to increment the risk of a subsequent infection in SLE. SInf are more common in male and Hispanics and is associated age, tobacco use and other co-morbidities. Antimalarials use exerts a time-dependent protective effect Disclosure of Interest None declared

AB0516 Thrombotic Thrombocytopenic Purpura in Patients from the SLE Registry of the Spanish Society of Rheumatology (Relesser)

Background In our area, SLE patients present haematologic manifestations in approximately 70% of cases1. Some of these manifestations are rare so there are no large series whose analysis can provide relevant information. Objectives To study the characteristics of patients with thrombotic thrombocytopenic purpura (TTP) in a large sample of SLE patients. Methods SLE patients from RELESSER database were studied. We analysed the clinical and serological SLE manifestations present at the 9 domains of the British Isles Lupus Assessment Group (BILAG) activity index, all of them before, during and after TTP diagnosis until the last patients assessment. We also studied activity (SELENA-SLEDAI) and damage (SLICC/ACR DI) indices in each one of those moments. We evaluated the treatment received, TTP recurrences and the number of deaths by this entity. Results 3,656 patients from 45 Rheumatology Units across Spain were studied. We found 19 cases of PTT (<1% of total). 100% were women, 94.7% Caucasian. Mean age (±SD) at diagnosis was 28.9±11.4 years. We divided the patients into 3 groups according to the chronology between diagnosis of TTP and SLE. In group 1 (G1) patients developed TTP and later SLE. In group 2 (G2) patients presented TTP and SLE simultaneously. In group 3 (G3) patients developedSLE and then TTP. According to this classification, 3, 5 and 11 patients were included in each group, respectively. At the time of TTP diagnosis the patients presented haemoglobin (g/dl) and platelets levels (mean number ± SD): In G1: 10±3.2 and 10,667±7,506; in G2: 7.7±2.1 and 25,200±38,590 and in G3: 7.4±1.8 and 22,909±18,387. Patients from G2, and particularly from G3, showed high SLE activity at PTT diagnosis (SLEDAI>6). Afterwards the patients maintained SLEDAI scores of 3.8±5.3 at G2 and 2.4±0.7 at G3. The number of therapy lines and the number of treatments administered was 2.8±2 and 5.4±2.9, respectively in G2, and 2.4±1.7 and 3.8±2.5 in G3, contrasting with G1 where the patients needed only 1 line ±0 of treatment and 2±1 drugs. The treatment most frecuently received by patients in G1 were glucocorticoids (GC)(100%), in G2 GC (100%), plasma exchange (PE) (80%) and cyclophosphamide (CyC)(60%); in G3 GC (81.8%), PE (72.7%) and CyC (41.8%). There were only recurrences and deaths in G3, 2 patients in each case. More detailed results of the analysis in each of the 3 groups are shown in table 1. Conclusions TTP is a rare event (<1%) in SLE. It can be severe and fatal. Because of this, PTT diagnosis should be suspected in all SLE patients who present anemia and thrombocytopenia and treatment should be started without delay. References Pego-Reigosa JM et al. Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus. Lupus. 2014. doi:10.1177/0961203314563818. Disclosure of Interest A. Lois: None declared, I. Rúa: None declared, V. delCampo: None declared, F. Lόpez: None declared, M. Galindo: None declared, J. Calvo: None declared, I. Hernández: None declared, M. Belmonte: None declared, C. Erausquin: None declared, E. Tomero: None declared, R. Blanco: None declared, V. Calvo: None declared, E. Uriarte: None declared, P. Vela: None declared, M. Freire: None declared, J. deToro: None declared, C. Montilla: None declared, E. Raya: None declared, A. Fernández: None declared, L. Horcada: None declared, J. Pego Grant/research support from: Work supported by Spanish Society of Rheumatology, FIS/ISCIII (PI11/02857), BIOCAPS from the EU 7th Framework Programme/REGPOT-2012-2013.1 (316265),GSK, Roche, Novartis,UCB.