Use of antimalarial drugs is associated with a lower risk of preeclampsia in lupus pregnancy: A prospective cohort study.

INTRODUCTION: Several factors have been associated with the development of preeclampsia in women with systemic lupus erythematosus (SLE). OBJECTIVE: To identify risk factors associated with preeclampsia in patients with SLE and its impact on fetal outcomes. PATIENTS AND METHODS: We studied a prospective cohort of pregnancies in women with SLE from January 2009 to December 2018. Demographic, clinical, serological and drug use characteristics were compared between patients who developed preeclampsia and those who did not, as well as the main neonatal outcomes. An adjusted logistic regression analysis was performed to identify factors potentially associated with preeclampsia. RESULTS: We studied 316 pregnancies of 20 or more weeks of gestation. A total of 46 pregnancies (14.5%) were complicated by preeclampsia. A higher frequency of active disease before pregnancy (24.4% vs 11.3%, P = .01) and history of lupus nephritis (56.5% vs 30.1%, P < .001) were found in those patients who developed preeclampsia compared to those who did not. Preeclampsia was associated with a higher rate of prematurity, births of very low birth weight, stillbirth, and neonatal death. The multivariate analysis showed that the activity of the disease before (relative risk [RR] 2.7, 95% CI 1.04-7.4, P = .04) and during pregnancy (RR 3.0, 95% CI 1.0-9.1, P = .04) was associated with the development of preeclampsia. The use of antimalarial drugs during pregnancy was associated with a lower risk of preeclampsia (RR 0.21, 95% CI 0.08-0.53, P < .001). CONCLUSIONS: Our study suggests that the use of antimalarial drugs during pregnancy reduces the risk of preeclampsia in lupus pregnancies.

Detection of autoantibodies to DSF70/LEDGFp75 in Mexican Hispanics using multiple complementary assay platforms.

PURPOSE: Antinuclear autoantibodies (ANA) targeting the dense fine speckled antigen DFS70, also known as lens epithelium-derived growth factor p75 (LEDGF/p75), are attracting attention due to their low frequency in systemic rheumatic diseases but increased frequency in clinical laboratory referrals and healthy individuals (HI). These ANA specifically recognize the stress protein DFS70/LEDGFp75, implicated in cancer, HIV-AIDS, and inflammation. While their frequency has been investigated in various ethnic populations, there is little information on their frequency among Hispanics/Latinos. In this study, we determined the frequency of anti-DFS70/LEDGFp75 autoantibodies in Mexican Hispanics using multiple detection platforms. METHODS: The frequency of anti-DFS70/LEDGFp75 antibodies was determined in 171 individuals, including 71 dermatomyositis (DM) patients, 47 rheumatoid arthritis (RA) patients, 30 obesity (OB) patients, and 23 HI. Antibody detection was achieved using four complementary assay platforms: indirect immunofluorescence, Western blotting, ELISA, and chemiluminescent immunoassay. RESULTS: We detected relatively low frequencies of anti-DFS70/LEDGFp75 antibodies in patients with DM (1.4%), RA (4.3%), and OB (6.6%), and elevated frequency (17.4%) in HI. A strong concordance between the different antibody detection platforms was observed. CONCLUSIONS: The low frequency of anti-DFS70/LEDGFp75 antibodies in Mexican patients with rheumatic diseases, but relatively higher frequency in HI, is consistent with previous observations with non-Hispanic populations, suggesting that geographic differences or ethnicity do not influence the frequency of these autoantibodies. Our results also highlight the importance of confirmatory assays for the accurate detection of these autoantibodies. Future studies with larger cohorts of healthy Hispanics/Latinos are needed to confirm if their anti-DFS70/LEDGFp75 antibody frequencies are significantly higher than in non-Hispanics.

Guías de práctica clínica para la atención del embarazo en mujeres con enfermedades reumáticas autoinmunes del Colegio Mexicano de Reumatología. Parte I / Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part I

Antecedentes. El embarazo en mujeres con enfermedades reumáticas autoinmunes se asocia a diversas complicaciones maternofetales. El desarrollo de guías de práctica clínica con la mejor evidencia científica disponible puede ayudar a homogeneizar la atención en estas pacientes. Objetivos. Proporcionar recomendaciones respecto al control prenatal, el tratamiento y el seguimiento más efectivo de la mujer embarazada con lupus eritematoso (LES), artritis reumatoide (AR) y síndrome por anticuerpos antifosfolípidos (SAF). Metodología. Para la elaboración de las recomendaciones se conformaron grupos nominales de expertos y se realizaron consensos formales, búsqueda sistematizada de la información, elaboración de preguntas clínicas, elaboración y calificación de las recomendaciones, fase de validación interna por pares y validación externa del documento final teniendo en cuenta los criterios de calidad del instrumento AGREE II. Resultados. Los grupos de trabajo contestaron las 37 preguntas relacionadas con la atención maternofetal en LES, AR y SAF, así como de fármacos antirreumáticos durante el embarazo y la lactancia. Las recomendaciones fueron discutidas e integradas en un manuscrito final y se elaboraron los algoritmos correspondientes. En esta primera parte se presentan las recomendaciones para mujeres embarazadas con LES. Conclusiones. La guía mexicana de práctica clínica para la atención del embarazo en mujeres con LES proporciona recomendaciones e integra la mejor evidencia disponible para el tratamiento y el seguimiento de estas pacientes (AU)

Background. Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. Objectives. To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphospholipid antibody syndrome (APS). Methodology. Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and grading of recommendations, internal validation by peers, and external validation of the final document. The quality criteria of the AGREE II instrument were followed. Results. The various panels answered the 37 questions related to maternal and fetal care in SLE, RA, and APS, as well as to the use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. We present the recommendations for pregnant women with SLE in this first part. Conclusions. We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with SLE integrate the best available evidence for the treatment and follow-up of patients with these conditions (AU)

Guías de práctica clínica para la atención del embarazo en mujeres con enfermedades reumáticas autoinmunes del Colegio Mexicano de Reumatología. Parte II / Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II

Antecedentes. El embarazo en mujeres con enfermedades reumáticas autoinmunes se asocia a diversas complicaciones materno-fetales. El desarrollo de guías de práctica clínica con la mejor evidencia científica disponible puede ayudar a homogeneizar la atención en estas pacientes. Objetivos. Proporcionar recomendaciones respecto al control prenatal, el tratamiento y el seguimiento más efectivo de la mujer embarazada con lupus eritematoso sistémico, artritis reumatoide (AR) y síndrome por anticuerpos antifosfolípidos (SAF). Metodología. Para la elaboración de las recomendaciones se conformaron grupos nominales de expertos y se realizaron consensos formales, búsqueda sistematizada de la información, elaboración de preguntas clínicas, elaboración y calificación de las recomendaciones, fase de validación interna por pares y validación externa del documento final teniendo en cuenta los criterios de calidad del instrumento AGREE II. Resultados. Los grupos de trabajo contestaron las 37 preguntas relacionadas con la atención materno-fetal en lupus eritematoso sistémico, AR y SAF, así como de fármacos antirreumáticos durante el embarazo y lactancia. Las recomendaciones fueron discutidas e integradas en un manuscrito final y se elaboraron los algoritmos correspondientes. En esta segunda parte se presentan las recomendaciones para mujeres embarazas con AR, SAF y el uso de fármacos antirreumáticos durante el embarazo y lactancia. Conclusiones. La guía mexicana de práctica clínica para la atención del embarazo en mujeres con AR y SAF integra la mejor evidencia disponible para el tratamiento y el seguimiento de estas pacientes (AU)

Background. Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. Objectives. To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus, rheumatoid arthritis (RA) and antiphospholipid syndrome (APS). Methodology. Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and staging of recommendations, internal validation by peers and external validation of the final document. The quality criteria of the AGREE II instrument were followed. Results. The panels answered 37 questions related to maternal and fetal care in lupus erythematosus, RA and APS, as well as for use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. In this second part, the recommendations for pregnant women with RA, APS and the use of antirheumatic drugs during pregnancy and lactation are presented. Conclusions. We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with RA and APS integrate the best available evidence for the treatment and follow-up of patients with these conditions (AU)

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part I.

BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphospholipid antibody syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and grading of recommendations, internal validation by peers, and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The various panels answered the 37 questions related to maternal and fetal care in SLE, RA, and APS, as well as to the use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. We present the recommendations for pregnant women with SLE in this first part. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with SLE integrate the best available evidence for the treatment and follow-up of patients with these conditions.

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II.

BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus, rheumatoid arthritis (RA) and antiphospholipid syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and staging of recommendations, internal validation by peers and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The panels answered 37 questions related to maternal and fetal care in lupus erythematosus, RA and APS, as well as for use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. In this second part, the recommendations for pregnant women with RA, APS and the use of antirheumatic drugs during pregnancy and lactation are presented. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with RA and APS integrate the best available evidence for the treatment and follow-up of patients with these conditions.

Predictores de respuesta al tratamiento en pacientes con nefritis lúpica / Prognostic factors for treatment response in patients with lupus nephritis

Objetivo: Identificar los factores asociados con la respuesta al tratamiento en pacientes con nefropatía lúpica. Material y métodos: Se analizó una cohorte retrospectiva de pacientes con lupus eritematoso sistémico (LES) y nefritis lúpica (NL) corroborada por biopsia, clasificada de acuerdo a la Organización Mundial de la Salud (OMS) de junio del 2001 a diciembre del 2008. Todos los pacientes recibieron terapia de inducción a la remisión y fueron seguidos al menos 2 años. Se correlacionaron variables clínicas y de laboratorio con potencial valor predictivo de respuesta terapéutica, a los 6, 12 y 24 meses. Resultados: Se incluyó a 168 pacientes, 84% mujeres. La tasa de respuesta al tratamiento fue del 69,2% a los 6 meses, el 86,9% a los 12 meses y el 79,7% a los 2 años. En el análisis multivariado se encontró que la edad > 25 a˜nos en el momento del diagnóstico de la NL y la presencia de microhematuria fueron variables asociadas con buena respuesta al tratamiento de inducción a la remisión. A los 12 meses, una epuración de creatinina basal < 30 ml/min se asoció a mala respuesta al tratamiento. Finalmente, a los 24 meses, el retraso en el tratamiento fue un factor predictor de mala respuesta y la presencia de una forma histológica proliferativa de NL y de C3 bajo se asociaron con buena respuesta al tratamiento. Conclusiones: Existen factores modificables con el tratamiento que pueden alterar la actividad inmunológica aberrante de la NF. Por ello, la intervención terapéutica intensa en los primeros 3 meses de inicio de la nefritis puede llevar a una respuesta favorable a los 2 años (AU)

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 < 30 ml/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 (AU)

Prognostic factors for treatment response in patients with lupus nephritis.

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.

Autoantibodies to transcription intermediary factor TIF1ß associated with dermatomyositis.

INTRODUCTION: Myositis specific autoantibodies are associated with unique clinical subsets and are useful biomarkers in polymyositis/dermatomyositis (PM/DM). A 120 kD protein recognized by certain patients with DM was identified and clinical features of patients with this specificity were characterized. METHODS: The 120 kD protein recognized by a prototype serum was purified and identified by mass spectrometry and immunological methods. Autoantibody to this 120 kD protein was screened in sera from 2,356 patients with various diagnoses from four countries, including 254 PM/DM, by immunoprecipitation of 35S-methionine labeled K562 cell extracts. Clinical information of patients with this specificity was collected. RESULTS: The 120 kD protein, which exactly comigrated with PL-12, was identified as transcription intermediary factor TIF1ß (TRIM28) by mass spectrometry and validated by immunoassays. By immunofluorescence, anti-TIF1ß positivity showed a fine-speckled nuclear staining pattern. Four cases of anti-TIF1ß were identified; all are women, one each in a Japanese, African American, Caucasian, and Mexican individual. Three had a diagnosis of DM and one case was classified as having an undifferentiated connective tissue disease with an elevated CPK but without significant muscle symptoms. This individual also had a history of colon cancer, cervical squamous metaplasia and fibroid tumors of the uterus. Myopathy was mild in all cases and resolved without treatment in one case. The anti-TIF1ß specificity was not found in other conditions. CONCLUSIONS: Anti-TIF1ß is a new DM autoantibody associated with a mild form of myopathy. Whether it has an association with malignancy, as in the case of anti-TIF1γ, or other unique features will need to be evaluated in future studies.

Impact of previous lupus nephritis on maternal and fetal outcomes during pregnancy.

Previous reports suggest that renal involvement before pregnancy or active renal disease during pregnancy may be associated with poor fetal and maternal outcomes in systemic lupus erythematosus (SLE) women. We report our experience of fetal and maternal complications in pregnant lupus women with and without previous lupus nephritis. We analyzed the clinical records of pregnant SLE patients attended in a tertiary reference center during a 5-year period. Patients were allocated into two groups according to the presence or absence of previous lupus nephritis. Women were evaluated monthly during pregnancy and at least 1 month postpartum. Maternal and fetal outcomes of pregnancy were abstracted. We included 95 pregnancies in 92 patients. Compared with pregnant women without lupus nephritis (n = 60), pregnancies with previous lupus nephritis (n = 35) were associated with a higher risk of maternal complications (88.5% vs. 43.3%, p = 0.00001), higher rate of lupus flares (54.2% vs. 25%, p = 0.004), and renal flares (45.7% vs. 6.6%, p = 0.00001), but most of which in most instances were reversible. On the other hand, fetal outcome was similar in both groups. Multivariate analysis showed that previous lupus nephritis and active lupus at conception were predictors of adverse maternal outcome. Pregnancies in women with previous lupus nephritis had a higher rate of maternal complications in comparison with those without. However, fetal prognosis was similar in both groups.