Multicenter study to assess presenteeism in systemic lupus erythematosus and its relationship with clinical and sociodemographic features.

Objective The aim of this study was to measure presenteeism (productivity impairment while the patient is at work) and the related risk factors in patients with systemic lupus erythematosus (SLE) from Argentina. Methods A total of 130 consecutive (1997 American College of Rheumatology (ACR) criteria) working patients with SLE were assessed using a standardized data collection form. Sociodemographic, disease and work-related variables were collected. The Work Productivity and Activity Impairment (WPAI) questionnaire was performed. Results Overall, 130 patients were included in the analysis; 91% were women, and the mean age was 39 years (range 19-77). A total of 43% were White, 43% Mestizo and 13% Amerindian. Overall, 38% were single and 38% were married. A total of 75% had more than 12 years of formal education. The median disease duration was 7 years (interquartile range 25-75 (IQR) 4-13). Median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 0 (IQR 0-2), and median Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC-SDI) score was 0 (IQR 0-1). Lupus quality of life (LupusQoL) domains scores were: physical health 87 (IQR 70-96), emotional health 78 (IQR 54-91), burden to others 75 (IQR 50-92), intimate relationships 87 (IQR 50-100), and body image 85 (IQR 70-100). Absenteeism was 8%, presenteeism was 19%, and overall work impairment (absenteeism + presenteeism) was 26%. In the multiple regression analysis, considering presenteeism as dependent variable, (adjusting by age, disease duration, >12 years of education, Non-white race, Visual Analogue Scale (VAS) pain, VAS fatigue, SLICC-SDI, LupusQoL, physical and emotional domains), we found that SLICC-SDI (odds ratio (OR) 1.68, confidence interval (CI) 1-2.7) and Non-white race (OR 3.27, CI 1.04-10) were related to presenteeism and >12 years of education (OR 0.30, CI 0.09-0.98) and higher scores of LupusQoL emotional health domain (OR 0.95, CI 0.92-0.98) were protective. Conclusions organ damage and Non-white race were significantly associated with presenteeism while >12 years of education and higher scores of LupusQoL emotional health domain were protective.

Association between severe disease course and nephritis with Q222R polymorphism in DNAse I gene among lupus patients: An Argentine multicenter study.

UNLABELLED: Objetives: Systemic lupus erythematosus is a multifactorial autoimmune disease and the glomerulonephritis is one of the most severe complications, which leads to severe persistent proteinuria, chronic renal failure, and end-stage renal disease. This multicenter study investigated the genetic associations of a non-synonymous single-nucleotide polymorphism in DNase I with the risk of lupus and its influence on development of nephropathy in an Argentinean population. METHODS: Using the Polymerase chain reaction restriction fragment length polymorphism method, the Q222R (+2373A→G; Gln244Arg) DNase I polymorphism was studied in 156 systemic lupus erythematosus patients and 170 healthy controls. RESULTS: Although no significant association between Q222R polymorphism and the risk of systemic lupus erythematosus was found, the presence of the A allele was associated with an increased risk for the development of nephropathy (p=0.019, Odd Ratio=2.196, 95 % confidence interval [1.135-4.247]) and a worse disease course [moderate disease course: p=0.006, Odd Ratio=3.250, 95% confidence interval (1.401-7.539); severe disease course: p=0.040, Odd Ratio=2.339, 95% confidence interval (1.040-5.260)]. CONCLUSIONS: A better understanding of the genetic basis of systemic lupus erythematosus will help in the development of new and more effectives strategies for the treatment of the disease in the future.

Validation of an Argentine version of Lupus Quality of Life questionnaire.

OBJECTIVE: To determine reproducibility and validity of an Argentine version of the Lupus Quality of Life questionnaire (LupusQoL) and to determine cut-off values in the questionnaire. MATERIALS AND METHODS: One hundred and forty-seven systemic lupus erythematosus patients (American College of Rheumatology 1982/1997) were assessed from April 2014 to July 2014. Demographic and socioeconomic variables were collected, as well as SELENA/SLEDAI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index Score, comorbidities and treatment data. Patients completed LupusQoL-Argentine version and European Quality of Life Questionnaire (EuroQoL-5D). Internal consistency and reliability were examined. Convergent validity with EuroQoL-5D was assessed through analysis of latent classes, which established homogeneous categories from the responses of each domain of LupusQoL and for the total. RESULTS: Out of 147 patients, 93.2% were female, mean age 36.4 ± 11.1 years, mean disease duration 2.7 ± 9 years, mean SELENA/SLEDAI 2.7 ± 3 points. The cut-off point that defined good or bad quality of life was 0.739 for EuroQoL 5D and 63 for LupusQoL. Cut-off values for each LupusQoL domain were also defined, creating two classes in each of them. There was moderate to high concordance to classify quality of life (Kappa = 0.74, 95% confidence interval = 0.54, 0.95). CONCLUSION: The Argentine version of LupusQoL is a valid, reliable and reproducible instrument to assess quality of life. In this study, cut-off points that allow the classification of patients regarding whether they have good or bad quality of life are established for the first time.

Características de los tratamientos biológicos en enfermedades reumáticas en Argentina: quinto informe del registro BIOBADASAR / Features of rheumatic diseases biological treatments in Argentina: BIOBADASAR fifth report

Introducción: El proyecto BIOBADASAR (Registro argentino deeventos adversos con tratamientos biológicos en reumatología)comenzó en agosto de 2010, para recabar información a largo plazosobre los eventos adversos en tratamientos biológicos en pacientescon enfermedades reumáticas en la práctica clínica cotidiana enArgentina.Pacientes y método: Se registraron datos de cada paciente,tratamientos y acontecimientos adversos relevantes o importantes.Los pacientes debían tener enfermedad diagnosticada y tratadacon un agente biológico. Cada caso se comparó con un control:un paciente con tratamiento no biológico con característicasdemográficas similares. Se analizaron los datos con análisis de lavarianza, con test de t de Student, Mann Whitney, test chi2, o testexacto de Fisher. El análisis de supervivencia de los tratamientoshasta su discontinuación o interrupción se realizó con el método deKaplan-Meier y test log-rank...

Background: BIOBADASAR (Argentine Registry of Adverse Eventsin Biological Treatments in Rheumatology) was started in August2010 to obtain long-term information of patients with rheumatic diseases,treatments and adverse events in everyday clinical practice.Patients and methods: Data on patients’ demographics,treatments and adverse events were collected. Patients had a diagnosisof a rheumatic disease and were treated with biological agent.To compare information, a control group was included, consisting ofpatients treated with similar demographic characteristics but treatedwith a non-biological agent. Data were analysed with Anova,Student´s t, Mann Whitney, chi2, Fisher´s exact tests, as appropriate.Survival analysis of treatments was performed with Kaplan-Meiercurves and log-rank test...

Concordancia de los nuevos criterios ACR/EULAR y los ACR 1980 para la clasificación de la esclerosis sistémica / Concordance of the new ACR/EULAR criteria and the ACR 1980 for the classification of systemic sclerosis

Objetivo: Evaluar cumplimiento, y así mismo concordancia y discordancia de los criterios de clasificación de Esclerosis Sistémica (ES) ACR/EULAR 2013 y ACR 1980 en pacientes con diagnóstico clínico de la enfermedad. Método: Se incluyeron 169 pacientes con diagnóstico de Esclerosis Sistémica. Resultados: El 72,2 por ciento cumplía los criterios ACR 1980, y el 99,4 por ciento (168 pacientes) cumplía los criterios ACR/EULAR 2013. La concordancia absoluta de toda la muestra fue 72,7 por ciento, para el subtipo limitado 35,2 por ciento, y 100 por ciento el difuso. Se subanalizaron los pacientes con limitada que sólo cumplían criterios ACR/EULAR 2013, y se comparó con el resto de las limitadas. Los primeros presentaron en forma estadísticamente significativa menor esclerodactilia distal a MCF, menor presencia de úlceras digitales y pitting scars, menor afectación intersticial pulmonar, y mayor daño microvascular en la capilaroscopia. Conclusión: Los nuevos criterios de clasificación de Esclerosis Sistémica serían más adecuados para detectar esclerodermias limitadas, siendo dicho hallazgo estadísticamente significativo.

Objective: To evaluate the performance, and likewise concordance and discordance of the classification criteria of Systemic Sclerosis ACR/EULAR 2013 and ACR 1980 in a group of patients with clinical diagnosis of SSc. Methods: We enrolled 169 patients with diagnosis of Systemic Sclerosis. Results: 72.2 percent met the 1980 ACR criteria, and 99.4 percent met the ACR/EULAR 2013 criteria. The absolute agreement of the entire sample was 72.7 percent, 35.2 percent for the limited subtype, and 100 percent for the diffuse. Those patients with limited subtype who only met the ACR/EULAR 2013 criteria were compared with the rest of limited patients. The first group had statistically significantly lower sclerodactyly distal to MCF, lower presence of digital ulcers and pitting scars, less interstitial lung involvement, and greater abnormal nail fold capillaries. Conclusion: The new classification criteria for systemic sclerosis seem to be more suitable for detecting limited scleroderma. In the present study, statistically significant discrepancy was found in the limited subtype.

Estudio multicéntrico de deterioro cognitivo en lupus eritematoso sistémico: ECLES / Multicenter study of cognitive decline in systemic lupus erythematousus: ECLES

Introducción: los pacientes lúpicos presentan un riesgo incrementado de deterioro cognitivo (DC) comparado con individuos sanos, el cual puede ser debido a múltiples causas. Objetivo: Describir la frecuencia y características del deterioro cognitivo en pacientes con lupus sin manifestaciones neuropsiquiátricas conocidas. Materiales y método: Se incluyeron pacientes de 16 a 55 años con diagnóstico de LES según criterios del Colegio Americano de Reumatología (ACR) de 1997. Se incluyeron test neuropsicológicos acordes a la propuesta del ACR y el cuestionario de Beck para evaluar depresión. Se definió DC a valores de <2 o más desvíos estándar comparada con la media de población normal en al menos un test. Se consideró focal cuando afectó una o más medidas de un dominio y multifocal en 2 o más dominios. Para comparar proporciones se utilizó prueba exacta de Fisher y para comparar variables numéricas se usó prueba de Kruskal-Wallis. Se consideró significativo un valor de p <0,05. Resultados: Se estudiaron 86 pacientes con lupus, el 90% de origen caucásico, 8% mestizos y 1% amerindio. El 82% alcanzó nivel secundario. La frecuencia de DC fue del 65% (56/86). Los dominios afectados: memoria 45%, funciones ejecutivas 30%, atención 29%, lenguaje 4,6%. Se detectó depresión en un 48% de los pacientes. Se analizaron diferentes factores de riesgo, sin hallar diferencias estadísticamente significativas a excepción de la etnia (p=0,02). Conclusión: Se halló una frecuencia elevada de deterioro cognitivo en pacientes con LES, los pacientes no caucásicos tuvieron mayor DC con diferencias significativas en comparación con los pacientes caucásicos.

Background: patients with systemic lupus erythematosus (SLE)have an increased risk of cognitive impairment (CI) compared tohealthy individuals and it may be due to multiple causes. Objective: To determine the frequency and characteristics of CI inlupus patients without known previous neuropsychiatric events. Methods: Patients aged 16 to 55 fulfilling the 1997 ACR criteria forSLE were included. The neuropsychological test battery proposedby the ACR was used to determine CI and Beck depression werealso assessed. CI was defined as values of ≤2 standard deviationscompared to the mean of the general population in at least one test. It was considered focal involvement if it affected one or more measuresof a single domain and multifocal if 2 or more domains wasaffected. To compare proportions, Fisher’s exact test was used andto compare numerical variables, Kruskal-Wallis. A value of p <0.05was considered significant. Results: 86 patients were evaluated, 90% were Caucasian, 8%mestizos and 1% Amerindian. 82% had high school. CI was foundin 65% of patients (56/86). The affected domains were: memory45%, executive functions 30%, attention 29% and language 4.6%. Depression was detected in 48% of patients. Different risk factorswere analyzed and found no statistically significant differences exceptfor ethnicity (p=0.02). Conclusion: A high frequency of CI was found in patients with SLE,non-Caucasian had higher CI with significant differences in comparisonwith Caucasian patients.

Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: data from a Latin American cohort.

OBJECTIVES: The objective of this paper is to assess the predictors of time-to-lupus renal disease in Latin American patients. METHODS: Systemic lupus erythematosus (SLE) patients (n = 1480) from Grupo Latino Americano De Estudio de Lupus (GLADEL's) longitudinal inception cohort were studied. Endpoint was ACR renal criterion development after SLE diagnosis (prevalent cases excluded). Renal disease predictors were examined by univariable and multivariable Cox proportional hazards regression analyses. Antimalarials were considered time dependent in alternative analyses. RESULTS: Of the entire cohort, 265 patients (17.9%) developed renal disease after entering the cohort. Of them, 88 (33.2%) developed persistent proteinuria, 44 (16.6%) cellular casts and 133 (50.2%) both; 233 patients (87.9%) were women; mean (± SD) age at diagnosis was 28.0 (11.9) years; 12.2% were African-Latin Americans, 42.5% Mestizos, and 45.3% Caucasians (p = 0.0016). Mestizo ethnicity (HR 1.61, 95% CI 1.19-2.17), hypertension (HR 3.99, 95% CI 3.02-5.26) and SLEDAI at diagnosis (HR 1.04, 95% CI 1.01-1.06) were associated with a shorter time-to-renal disease occurrence; antimalarial use (HR 0.57, 95% CI 0.43-0.77), older age at onset (HR 0.90, 95% CI 0.85-0.95, for every five years) and photosensitivity (HR 0.74, 95% CI 0.56-0.98) were associated with a longer time. Alternative model results were consistent with the antimalarial protective effect (HR 0.70, 95% CI 0.50-0.99). CONCLUSIONS: Our data strongly support the fact that Mestizo patients are at increased risk of developing renal disease early while antimalarials seem to delay the appearance of this SLE manifestation. These data have important implications for the treatment of these patients regardless of their geographic location.

Pulmonary involvement of systemic lupus erythematosus: analysis of 90 necropsies.

Pleuropulmonary manifestations of systemic lupus erythematosus (SLE) have been reported to be of variable prevalence, depending on the diagnostic methods used. The objective of this study was to determine the anatomopathological prevalence and the nature of lung involvement associated with SLE and to define if there were differences in the grade and type of pulmonary involvement in patients who had died at different time periods, before or after 1996. Complete autopsy studies of 90 patients with SLE diagnosis carried out between 1958 and 2006 and their clinical records were studied. All patients fulfilled the American College of Rheumathology (ACR) diagnostic criteria for SLE. Two groups of patients were analyzed: patients who had died before 1996 and those deceased in 1996-2006. Some pleuropulmonary involvement was detected in 97.8% of the autopsies. The most frequent findings were pleuritis (77.8%), bacterial infections (57.8%), primary and secondary alveolar haemorrhages (25.6%), followed by distal airway alterations (21.1%), opportunistic infections (14.4%) and pulmonary thromboembolism (7.8%), both acute and chronic. No cases of acute or chronic lupus pneumonitis were found. Opportunistic lung infections were invasive aspergillosis, disseminated strongyloidiasis, mucormicosis and Pneumocystis carinii. Only three of 23 patients with alveolar haemorrhage showed capillaritis. The four patients with primary pulmonary hypertension (PHT) had plexiform lesions. Deceased patients' age at death (46.09 +/- 11.01 vs 30.3 +/- 11.5 years, P < 0.0001) as well as survival time from diagnosis date (11.8 +/- 11.2 vs 4.4 +/- 4.9 years, P < 0.0001) in the second time period evaluated were significantly higher. However, there were no statistically significant differences in the prevalence of any of the pulmonary manifestations. Sepsis was considered the major cause of death without significant differences in both groups. Our results show that pulmonary manifestations directly caused by systemic lupus erythematosus are very uncommon and that their prevalence has not changed in the past 10 years. Pulmonary infection is still the most frequent affection, and it is an important cause of death in patients with lupus.

[Catastrophic antiphospholipid syndrome. Communication of 2 forms of presentation]. / Síndrome antifosfolipídico catastrófico. Comunicación de dos formas de presentación.

Antiphospholipid syndrome is characterized by recurrent fetal loss, arterial and venous thromboses, thrombocytopenia and circulating antiphospholipid antibodies. Few patients have a rapidly progressive, fatal outcome. We report two young patients with systemic lupus erythematosus and antiphospholipid antibodies who died after a short course of disease. Although clinical and laboratory findings differed in both patients--small vessel thromboses and microangiopathic hemolytic anemia mimicking thrombotic thrombocytopenic purpura predominated in one of the patients while small and medium size vessel thromboses without hemolysis were present in the other case--autopsy revealed widespread visceral thromboses in both of them, features consistent with a diagnosis of catastrophic antiphospholipid syndrome. This syndrome has not been reported to occur in association with Pneumocistis carinii pneumonia as we describe in one of our patients.

Síndrome antifosfolipídico catastrófico. Comunicación de dos formas de presentación. / [Catastrophic antiphospholipid syndrome. Communication of 2 forms of presentation]

Antiphospholipid syndrome is characterized by recurrent fetal loss, arterial and venous thromboses, thrombocytopenia and circulating antiphospholipid antibodies. Few patients have a rapidly progressive, fatal outcome. We report two young patients with systemic lupus erythematosus and antiphospholipid antibodies who died after a short course of disease. Although clinical and laboratory findings differed in both patients--small vessel thromboses and microangiopathic hemolytic anemia mimicking thrombotic thrombocytopenic purpura predominated in one of the patients while small and medium size vessel thromboses without hemolysis were present in the other case--autopsy revealed widespread visceral thromboses in both of them, features consistent with a diagnosis of catastrophic antiphospholipid syndrome. This syndrome has not been reported to occur in association with Pneumocistis carinii pneumonia as we describe in one of our patients.

Increased superoxide production by polymorphonuclear leukocytes in systemic lupus erythematosus.

Normal and lupus PMN show an enhancement in superoxide production in vitro when stimulated with lupus serum. When N-formyl-methionyl-leucyl-phenylalanine (FMLP) was used, lupus PMN showed an O2- production of 2.1 nmol/min/10(7) cells, which is 5.2 times the response of normal PMN stimulated by FMLP. Our results show the existence of serum factors in SLE patients that can stimulate O2- production by PMN. Lupus neutrophils showed an increased response to membrane stimuli such as FMLP, capable of triggering the cell respiratory burst. Lupus neutrophils appeared more responsive to membrane stimuli. The serum and cellular factors seemed to indicate an increase rate of superoxide production by PMN in lupus patients, which could be relevant factors in the development of vasculitis and tissue damage.

[Erythrocyte CR1 receptor reactivity in patients with systemic lupus erythematosus]. / Reactividad del receptor eritrocitario CR1 en pacientes con lupus eritematoso sistémico.

Erythrocytes from 42 systemic lupus erythematosus (SLE) patients and 80 healthy volunteers were tested for the immunoadherence (CR1) receptor reactivity, observed by hemagglutination (IAHA) when incubating erythrocytes and aggregated human gamma-globulin (AHGG)-complement in appropriate proportions. Reactivity was expressed as the highest two-fold dilution of AHGG (2n) that induced hemagglutination. Erythrocytes of 15 SLE patients (35.7%) showed reactivity compared with 70 normal controls (87.5%). Both groups showed a trimodal distribution of IAHA titers in accordance with the three phenotypic groups described by other authors. Of the healthy population 72.5% belong to the intermediate reactivity mode (2(6) to 2(8)) and 64.3% of the SLE patients to the low reactivity group (negative). There was no correlation between CR1 defective expression and conventional activity parameters. This erythrocyte receptor involved in the immunocomplex clearance process, which constitutes 95% of the circulating CR1, is another factor that contributes to the pathophysiology of the disease when it is defective.

Reactividad del receptor eritrocitario CR1 en pacientes con lupus eritematoso sistémico. / [Erythrocyte CR1 receptor reactivity in patients with systemic lupus erythematosus]

Erythrocytes from 42 systemic lupus erythematosus (SLE) patients and 80 healthy volunteers were tested for the immunoadherence (CR1) receptor reactivity, observed by hemagglutination (IAHA) when incubating erythrocytes and aggregated human gamma-globulin (AHGG)-complement in appropriate proportions. Reactivity was expressed as the highest two-fold dilution of AHGG (2n) that induced hemagglutination. Erythrocytes of 15 SLE patients (35.7

) showed reactivity compared with 70 normal controls (87.5

). Both groups showed a trimodal distribution of IAHA titers in accordance with the three phenotypic groups described by other authors. Of the healthy population 72.5

belong to the intermediate reactivity mode (2(6) to 2(8)) and 64.3

of the SLE patients to the low reactivity group (negative). There was no correlation between CR1 defective expression and conventional activity parameters. This erythrocyte receptor involved in the immunocomplex clearance process, which constitutes 95

of the circulating CR1, is another factor that contributes to the pathophysiology of the disease when it is defective.

[Neutrophil-dependent inflammatory reactions in systemic lupus erythematosus]. / Reacciones inflamatorias neutrofilo-dependientes en Lupus Eritematoso Sistémico.

We studied the possible role of polymorphonuclear neutrophil (PMN) aggregation in Systemic Lupus Erythematosus (SLE) by the capacity of sera from 32 lupus patients to induce in vitro normal PMN aggregation. Neutrophil aggregating activity (NAA) in this group was significantly greater than that found in 8 inactive SLE patients and in 8 controls. In patients with SLE, there was a positive correlation between disease severity and the quantitative measure of NAA. High levels of NAA were particularly characteristic of central nervous system SLE. These data suggest that the formation of intravascular leukoaggregates may contribute to morbidity in SLE. Normal PMN increase their spontaneous superoxide anion production (0.21 nmol/min 10(7) PMN) when stimulated with sera from SLE patients. Lupus PMN also show an enhancement of 100% in superoxide production in vitro when stimulated with lupus sera. When N formyl methionine leucyl phenylalanine (FMLP) was used, lupus PMN showed an O2-production of 2.1 nmol/min 10(7) which is 5-fold the response of normal PMN stimulated by FMLP. Our results show the existence of seric factors in SLE patients that can stimulate O2-production by PMN. Lupus neutrophils show an increased response to membrane stimuli such as FMLP, capable of triggering the respiratory burst. Lupus neutrophils appear more responsive membrane stimuli such as FMLP, capable of triggering the respiratory burst. Lupus neutrophils appear more responsive to membrane stimuli. The seric and the cellular factors seem to indicate an increased rate of superoxide production by PMN in SLE patients, which can be relevant to vasculitis and tissue damage.

Reacciones inflamatorias neutrofilo-dependientes en Lupus Eritematoso Sistémico. / [Neutrophil-dependent inflammatory reactions in systemic lupus erythematosus]

We studied the possible role of polymorphonuclear neutrophil (PMN) aggregation in Systemic Lupus Erythematosus (SLE) by the capacity of sera from 32 lupus patients to induce in vitro normal PMN aggregation. Neutrophil aggregating activity (NAA) in this group was significantly greater than that found in 8 inactive SLE patients and in 8 controls. In patients with SLE, there was a positive correlation between disease severity and the quantitative measure of NAA. High levels of NAA were particularly characteristic of central nervous system SLE. These data suggest that the formation of intravascular leukoaggregates may contribute to morbidity in SLE. Normal PMN increase their spontaneous superoxide anion production (0.21 nmol/min 10(7) PMN) when stimulated with sera from SLE patients. Lupus PMN also show an enhancement of 100

in superoxide production in vitro when stimulated with lupus sera. When N formyl methionine leucyl phenylalanine (FMLP) was used, lupus PMN showed an O2-production of 2.1 nmol/min 10(7) which is 5-fold the response of normal PMN stimulated by FMLP. Our results show the existence of seric factors in SLE patients that can stimulate O2-production by PMN. Lupus neutrophils show an increased response to membrane stimuli such as FMLP, capable of triggering the respiratory burst. Lupus neutrophils appear more responsive membrane stimuli such as FMLP, capable of triggering the respiratory burst. Lupus neutrophils appear more responsive to membrane stimuli. The seric and the cellular factors seem to indicate an increased rate of superoxide production by PMN in SLE patients, which can be relevant to vasculitis and tissue damage.