Ulises Angeles

Prolactin Levels Are Associated with Lupus Activity, Lupus Anticoagulant, and Poor Outcome in Pregnancy

Abstract:  High prolactin (PRL) levels seem to be associated with active systemic lupus erythematosus (SLE) during pregnancy. However, the association of activity, lupus anticoagulant (LA), and pregnancy outcome has not been analyzed. The objective of this study was to analyze the association among SLE activity, LA, and maternal–fetal outcome. We studied 15 pregnant SLE patients (ACR criteria), 4 of them with associated antiphospholipid syndrome (APS), and 9 healthy pregnant women. All patients were evaluated monthly with the following determinations: (a) SLE activity using modified‐systemic lupus activity measurement (m‐SLAM), (b) LA, and (c) PRL serum levels. Healthy controls were evaluated each trimester. Prematurity, fetal loss, low birth weight, and preeclampsia were evaluated. Chi‐square test, Fishers exact test, Students t‐test, Pearson correlation, and ANOVA were performed. The mean age of SLE patients was 30 ± 4.9 years and 27.1 ± 3.7 years in controls. High PRL levels were found during the second and third trimester in SLE patients in comparison with controls (186.2 ± 54.02 ng/mL versus 119.6 ± 31.1 ng/mL (P < 0.01) and 177.4 ± 48.6 ng/mL versus 158.3 ± 31.5 ng/mL. A significant linear correlation between PRL, m‐SLAM, and LA in association with poor maternal–fetal outcome was observed. LA and PRL conferred risk for poor pregnancy outcome. Our study indicates for the first time a strong association among PRL, LA, SLE activity, and poor pregnancy outcome. Close rheumatologic and obstetric monitoring is mandatory in SLE pregnancy in order to avoid obstetric complications.

Primigravida is associated with flare in women with systemic lupus erythematosus

The objective of this study was to identify risk factors associated with flare during pregnancy in women with systemic lupus erythematosus (SLE). We performed a retrospective analysis of pregnant women with SLE in a referral hospital. Flare was considered according to predetermined definitions. We analyzed 15 clinical, biochemical and immunological variables with a potential predictive value for relapse during pregnancy. We included 124 lupus pregnancies in 120 women. The relapse rate during pregnancy was 37.9% (47 episodes). The most common manifestations of flare were renal, joint, cutaneous and hematological. Patients with flare during pregnancy developed a higher frequency of preeclampsia and preterm delivery. In multivariate analysis, primigravida was a risk factor associated with any type of flare during pregnancy (OR 2.3, 95% CI 0.99–5.52, p = 0.05); on the other hand, primigravida (OR 3.6, 95% CI 1.19–11.3, p = 0.02), activity prior to pregnancy (OR 3.7, 95% CI 0.97–14.1, p = 0.05), and previous renal disease (OR 5.8, 95% CI 1.95–17.6, p = 0.001) were the principal risk factors associated with renal flare. The first pregnancy in women with SLE is associated with any type of flare. Disease activity is associated with preeclampsia and preterm delivery. Close monitoring is mandatory to identify relapses and timely treatment.

Clinical significance of antiphospholipid syndrome nephropathy (APSN) in patients with systemic lupus erythematosus (SLE)

UNLABELLED Antiphospholipid syndrome nephropathy (APSN) is now a well recognized vaso-occlusive renal lesion associated with acute thrombosis and chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. Our objective was to evaluate the prevalence and clinical significance of APSN in patients with Systemic Lupus Erythematosus (SLE). METHODS Kidney biopsy specimens obtained from 162 patients with lupus glomerulonephritis were retrospectively examined for the presence of APSN. Clinical and laboratory data obtained at the time of kidney biopsy and during a mean follow-up of 7 years were recorded. In cases for which serial kidney biopsy specimens were available, the evolution of APSN was examined. RESULTS We found APSN in 17 (10.4%) patients with lupus glomerulonephritis (GN), 12 with focal or proliferative lesions. Both activity and chronicity indexes were higher in patients with APSN when compared with lupus nephritis without APSN. Patients with APSN had a higher frequency of hypertension and elevated serum creatinine levels at the time or kidney biopsy, as well as a higher frequency of rapidly progressive GN, nephrotic syndrome and death at the end of the follow-up. Anticardiolipin antibodies were found in 52% of those with APSN and in 27% of those without APSN. Serial kidney biopsy specimens were available from 18 patients. An increase of glomerular sclerosis was found in the second biopsy particularly in those patients with APSN in the first biopsy. CONCLUSIONS APSN is a risk factor that contributes to an elevated prevalence of hypertension, elevated serum creatinine, nephrotic syndrome and increased glomerular sclerosis. APSN should be included in the classification criteria of APS, and the use of appropriate anticoagulant therapy should be tested.

Active haematological manifestations of systemic lupus erythematosus lupus are associated with a high rate of in-hospital mortality.

The aim of this study was to estimate the impact of the haematological manifestations of systemic lupus erythematosus (SLE) on mortality in hospitalized patients. For that purpose a case–control study of hospitalized patients in a medical referral centre from January 2009 to December 2014 was performed. For analysis, patients hospitalized for any haematological activity of SLE (n = 103) were compared with patients hospitalized for other manifestations of SLE activity or complications of treatment (n = 206). Taking as a variable outcome hospital death, an analysis of potential associated factors was performed. The most common haematological manifestation was thrombocytopenia (63.1%), followed by haemolytic anaemia (30%) and neutropenia (25.2%). In the group of haematological manifestations, 17 (16.5%) deaths were observed compared to 10 (4.8%) deaths in the control group (P < 0.001). The causes of death were similar in both groups. In the analysis of the variables, it was found that only haematological manifestations were associated with intra-hospital death (odds ratio 3.87, 95% confidence interval 1.8–88, P < 0.001). Our study suggests that apparently any manifestation of haematological activity of SLE is associated with poor prognosis and contributes to increased hospital mortality.

Mono-organic versus Multi-organic Involvement in Primary Antiphospholipid Syndrome

Abstract: The prevalence of mono‐organic and multi‐organic involvement during long‐term follow‐up in patients with primary antiphospholipid syndrome (pAPS) was investigated. We studied 60 pAPS patients followed up at least 5 years. Patients with associated systemic lupus erythematosus were excluded. All patients received oral anticoagulant therapy. A diagnosis of mono‐organic involvement was considered when one organ was affected exclusively, and multi‐organic involvement was considered when two or more organs became affected during follow‐up. Average age at diagnosis was 32.9 ± 12.4 years, 40 subjects were female and 20 male, and mean disease evolution totaled 11.5 ± 4.5 years. The mean number of clinical events was 3.75 ± 1.87. Among patients, immunoglobulin G anticardiolipin (IgM aCL) titers totaled 50 ± 40.3 IgG phospholipid units, and IgM aCL titers totaled 47.3 ± 35.4 IgM phospholipid units. The most frequent clinical manifestations at study onset were deep venous thrombosis, stroke, pulmonary thromboembolism, fetal loss, and pre‐eclampsia. At the beginning of follow‐up, 46 patients had mono‐organic involvement and 14 had multi‐organic involvement (P= 0.0001). In contrast, at the end of the study, only 8 patients still had mono‐organic involvement, leading to deep venous thrombosis (n= 3), stroke (n= 3), and retinal thrombosis (n= 2) (P= 0.0001). Kaplan‐Meier analysis showed that the probability of remaining with mono‐organic involvement decreased throughout the cumulative years, especially during the first 3. The hazard risk ratio for developing multi‐organic involvement was 1.47 patients per year. In conclusion, PAPS is a chronic disorder with unpredictable clinical course and multi‐organic involvement, especially during the first years. The conversion to multi‐organic involvement supports the concept that pAPS is a systemic autoimmune disease.

Predictores de respuesta al tratamiento en pacientes con nefritis lúpica

OBJECTIVE To identify prognostic factors associated with response to induction therapy in lupus nephritis (LN) according to the stage of treatment. MATERIAL AND METHODS We analyzed a retrospective cohort of patients of systemic lupus erythematosus (SLE) with biopsy-proven LN from January 2001 to December 2008. LN was classified according to WHO. All patients received induction therapy and had a minimum follow-up period of two years. We analyzed 18 clinical and laboratory variables that potentially have predictive value for response to therapy. We identified predictors of therapeutic response at 6, 12 and 24 months by univariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. RESULTS We reviewed the clinical records of 168 patients, 141 female (84%). The response rate was 69% at 6 months, 86.9% at 12 months and 79.7% at 24 months. Multivariate analysis found that > 25 years of age at diagnosis of LN and the presence of microhematuria were factors associated with good response to induction treatment. At 12 months, baseline creatinine clearance < 30ml/min was associated with a poor response to treatment. Finally at 24 months, delay in treatment was a predictor of poor response to treatment and the presence of a histological proliferative NL and low C3 were associated with good response to treatment. CONCLUSIONS There are treatment-modifiable factors that can alter aberrant immunologic activity of NF. Therefore, intensive early treatment of lupus nephritis is associated with favorable response to two years.

SAT0024 Mortality in Hospitalized Patients with Systemic Lupus Erythematosus and Hematologic Manifestations: A Case-Control Study

Background Hematological complications are frequent in systemic lupus erythematosus (SLE) and are considered as good prognosis compared to other organs involvement. However, little is known about the impact of these manifestations in hospital mortality in SLE patients. Objectives To determine the prognostic impact of hospitalized patients with SLE with and without hematological manifestations Methods We performed a retrospective case-control study nested in a cohort of patients hospitalized for active SLE (ACR 1997) from January 2009 to July 2012. Case definition: patients with hematologic manifestation attributable to SLE. Control definition: SLE patient without hematologic manifestation. Severe hematologic manifestation was defined as follows: thrombocytopenia <30,000 K/μL, neutropenia <500 K/μL and hemolytic anemia with <7g/dL. We excluded cases associated with drug toxicity. Information was obtained from medical records of patients during first admissions and included clinical, laboratory and immunological variables. Statistical analysis included descriptive statistics, Students t-test, standard chi-square according to the behavior of the variables; we identified predictors of hospital death by multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. Results We studied 83 cases (mean age 33.3±14.2 years) and 123 controls (mean age 30.5±11.6 years). There were no differences in immune variables. Thrombocytopenia (severe in 62%) was the most common hematological feature followed by hemolytic anemia (severe in 37%) and neutropenia (severe in 89%). Renal (65% vs 45%) and neurologic (26% vs 10%) manifestations were more prevalent in control group. The mean SLEDAI in cases on admission was 9.7±6.8 and in controls 11.0±7.1 (p=0.2). The number of organs involved in the cases was 2±1 and 3±1 control group (p<0.01). There were 24 hospital deaths, 19 (23%) in cases and 5 (4.1%) in controls (p<0.01). The main causes of death in the cases were: disease activity, gastrointestinal hemorrhage, stroke, pneumonia and sepsis and in the controls, they were diffuse alveolar hemorrhage, infections and kidney failure. In multivariable analysis the main variables associated with mortality in cases were hematologic SLE (OR 9.5, 95% CI 3.3-27.6, p<0.01) and low C3 (OR 3.5, 95% CI 1.08-11.8, p=0.04). Conclusions Our study suggests that hospitalized SLE patients with hematologic complications have a higher mortality in comparison with non-hematologic SLE. The number of organs involved and SLEDAI score on admission had no impact on mortality. The presence of hematologic activity and low C3 are factors associated with mortality. The hematologic abnormalities in SLE should have higher scores on indexes of disease activity. References Hepburn AL, Rheumatology 2010;49:2243-2254. Zhao H, Platelets 2010;21:380-385. Jallouli M, Lupus 2012;21:682-687 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5170

SAT0235 Predictors of flare during pregnancy in women with systemic lupus erythematosus

Background Woman with systemic lupus erythematosus (SLE) have 2 to 3 times higher risk of reactivation during pregnancy. However, the predictive factors of lupus flare in pregnancy are not completely elucidated. Objectives To identify predictors of flare in pregnant women with SLE. Methods We reviewed clinical records of a cohort of pregnant women with SLE (ACR 1982, 1997) treated in our Clinic of Pregnancy and Rheumatic Diseases in a tertiary referral center for the period January 2005 to June 2011. Patients were evaluated at least once during each trimester and once postpartum. Primary endpoint was lupus flare including specific skin lesions, arthritis, hematological, neurologic, cardiopulmonary and renal manifestations. We analyzed 15 clinical and laboratory variables that potentially have predictive value for lupus flare during pregnancy, including age, duration of disease, activity of SLE before pregnancy, renal function, organ involvement, parity, drug use and immunological parameters. For analysis each pregnancy was included as an independent event and these were divided into 2 groups: those of mothers who relapsed and those who did not. Statistical analysis included descriptive statistics, chi square, Student t test, bivariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. Results We studied 124 pregnancies in 120 women with a mean age of 26.5±5.1 years at time of pregnancy, with an mean of SLE evolution 5.2±4.1 years, 45 (36.2%) patients had lupus nephritis before pregnancy, 16 (12.9%) women had SLE activity before pregnancy, 47 (37.9%) women had at least one episode of flare during pregnancy. The significant variables associated with lupus flare during pregnancy in bivariate and multivariate analysis are shown in the table. Variable Bivariate analysis Multivariate analysis OR 95% CI P OR 95% CI P Age>30 years 0.41 0.175-0.982 0.04 0.54 0.20-1.45 0.22 Primiparous 3.08 1.45-6.56 0.00 2.34 0.99-5.52 0.05 Previous nephritis 2.06 0.973-4.385 0.05 Hypocomplementemia 9.97 1.16-7.58 0.01 2.54 0.94-6.84 0.06 The live birth rate was similar in both groups (80.9% vs 87%, p=0.35); on the other hand, the rate of prematurity was higher (55.3% vs 35.1%, p=0.02) with fewer weeks of gestation (34.6±3.9 vs 35.8±3.4, p=0.009) in women who relapsed. Conclusions According to the experience of our center, primiparous woman with SLE and hypocomplementemia before conception (lupus subclinical activity data) have a higher risk of relapse during pregnancy. Disclosure of Interest None Declared

SAT0184 Predictors of response to induction therapy in lupus nephritis

Background Several prognostic factors have been described in lupus nephritis, which vary depending on the population studied. Few studies have examined these factors in relation to different stages of treatment. Objectives To identify prognostic factors associated with response to induction therapy in LN according to the stages of treatment. Methods We performed a retrospective case-control study nested in a cohort of patients with systemic lupus erythematosus (SLE) with biopsy-proven LN according to WHO, in a period from January 2001 to December 2008. All patients received induction therapy remission and had a minimum follow-up period of two years. Patients were divided in 2 groups: group 1, responders (presence of inactive sediment, proteinuria <0.5 g/day, and estable renal function) and group 2: non-responders (active sediment, proteinuria >0.5 g/day, and decrease renal function) at 6, 12, and 24 months. We analyzed 18 clinical and laboratory variables that potentially have predictive value for response to therapy including age, gender, duration of SLE, duration of LN, histologic type, delay in treatment, biochemical (serum creatinine, urinary active sediment, creatinine clearance, proteinuria), and immunological parameters (complement C3, C4 and anti-dsDNA antibodies). We identified predictors of therapeutic response at 6, 12 and 24 months by univariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. Results We reviewed clinical records of 168 patients, 141 of female (84%), with average age at diagnosis of LN of 30.4±10.6 years, the mean time of evolution of SLE until LN diagnosis was 28.0±48.8 months. LN was initial manifestation of SLE in 94 (56.5%) patients, renal biopsy showed: type II in 33 patients (19.6%), class III in 28 (16.6%), class IV in 92 (54.7%), class V in 7 (10.2%) and a combination in 7 (10.2%). One-hundred and thirteen (67%) patients received pulses of cyclophosphamide as induction therapy, the response rate was 69% at 6 months, 86.9% at 12 months and 79.7% at 24 months. Multivariate analysis with lack of therapeutic response as the dependent variable is shown in the following table: OR IC 95% P 6 months Age >25 years 0.22 0.10-0.48 0.00 Male gender 2.08 0.81-5.34 0.13 Creatinine >1.4 mg/dL 2.29 0.91-5.78 0.08 Eritrocituria 0.35 1.28-11.43 0.02 12 months Male gender 2.67 0.90-7.93 0.08 Creanitine clearance <30 ml/min 3.82 1.28-11.43 0.02 24 months Nephritis III/IV 0.28 0.09-7.93 0.02 Treatment delay 5.36 1.36-21.14 0.02 Eritrocituria 2.49 0.72-8.57 0.15 Hypocomplementemia C3 0.34 0.12-0.99 0.05 Conclusions The main predictor of poor therapeutic response at 24 months is the delay in treatment. At 12 months is low creatinine clearance. Patients younger than 25 years and microhematuria are the best responders to treatment at 6 months. Male gender and elevated creatinine and hypocomplementemia were not factors of poor therapeutic response. Early treatment of lupus nephritis is associated with favourable response to two years. Disclosure of Interest None Declared

Influencia de la infección de vías urinarias no complicada en la frecuencia de exacerbaciones en pacientes con nefritis proliferativa difusa lúpica

Objetivo: Determinar si la infeccion de vias urinarias (IVU) es un indicador de retraso en el tratamiento inmunodepresor y de recaida renal en pacientes con nefritis lupica. Pacientes y metodos: Se analizo a pacientes con nefritis lupica proliferativa difusa que recibieron tratamiento con ciclofosfamida intravenosa durante, al menos, 6 meses. Al cabo de ese tiempo se realizo un seguimiento prospectivo asignando a los pacientes a uno de 2 grupos: grupo I (pacientes que durante el seguimiento desarrollaron IVU), y grupo II (grupo control, pacientes sin infeccion). Se evaluaron bimestralmente la funcion renal y el numero de recaidas durante un ano de seguimiento. Para el analisis estadistico, se emplearon la prueba de la t de Student, la prueba de la x2, el test de Fisher (cuando se requiera) y el analisis bivariado. Resultados: Se incluyo a 50 pacientes, 25 en cada grupo. Los casos del grupo I correspondieron a IVU no complicada. La edad promedio fue de 30,07 ± 8,15, y el 82% eran mujeres. El uropatogeno descrito con mas frecuencia fue Escherichia coli (73%). La presencia de IVU determino la interrupcion temporal del tratamiento en 19 casos (76%), mientras que en el grupo sin IVU esto ocurrio solo en 3 pacientes (12%), por otras causas, como leucopenia grave, hipersensibilidad y sintomas gastrointestinales graves (odds ratio = 23,22; intervalo de confianza del 95%, 5,26-105,1; p = 0,001). Durante el ano de seguimiento, en el grupo I, el 90,9% alcanzo la remision parcial en los primeros 3 meses de seguimiento y el 35% logro la remision completa despues de un ano; en el grupo II, los porcentajes de remision fueron del 85 y el 63%, respectivamente. En el grupo I se observo un incremento en la albuminuria (p < 0,05), persistencia de hipocomplementemia y titulos elevados de anticuerpos anti-ADN. En este grupo se encontraron 18 exacerbaciones y en el grupo control, 9. Conclusiones: En pacientes con nefritis lupica proliferativa difusa, la presencia de IVU no complicada se asocia a un retraso en el tratamiento inmunodepresor y a un incremento en las recaidas renales.OBJECTIVE In patients with proliferative lupus nephritis treated with IV cyclophosphamide, analyze urinary tract infection (UTI) as a cause of treatment delay and renal relapses, compared with lupus nephritis patients without infection. PATIENTS AND METHODS We studied SLE patients (ACR criteria) with renal biopsy showing nephritis class IV. All patients received monthly intravenous cyclophosphamide (CYC) treatment during 6 months. Thereafter patients were assigned to 2 groups: patients who developed UTI, and those who did not; renal function tests, UTI and renal relapses were bimonthly evaluated during one year (follow-up period). To analyze data, t student test, χ(2), Fisher exact (when appropiate), and bivariate analysis, were performed. RESULTS We studied 50 patients, 25 with UTI (Group I) and 25 without UTI (G-II).The mean age was 30.07 ± 8.15 years, 82% were female. E. coli was the pathogen most frequently isolated (73%). UTI (G-I) was the cause for treatment delay in 19 cases (76%), compared with 3 patients (12%) in G-II whose treatment was delayed because of some other causes (severe leucopenya, hypersensibility and gastrointestinal side effects) (OR 23.22, 95% CI, 5.26-105.1; P=001). During the follow up, 90.9% of patients in G-I reached partial or complete renal remission within 3 months, but only 35% mantained remission after the year of follow up. Meanwhile, patients in G-II had complet and partial renal remission of 85% and 63%, respectively. In the first group we observed persistent albuminuria (P<05), low complement levels and high ab-dsDNA titers. Renal flares were present in 18 patients in G-I and 9 in G-II. CONCLUSIONS UTI in lupus nephritis patients has a negative impact. It leads to delayed CYC therapy and to a higher renal flare rate.