Search

Objective: The present study aimed to analyse the frequency of premature rupture of membranes (PROMs) among 190 women with systemic lupus erythematosus (SLE) followed up at the Hospital Universitário Pedro Ernesto from 2011 to 2018 and to review the literature on PROM in patients with SLE., Methods: A cohort study of SLE patients was conducted by analysing the following variables: sociodemographic characteristics, clinical manifestations of lupus, modified disease activity index for pregnancy, drugs used during pregnancy, intercurrent maternal infections and obstetric outcomes. Additionally, seven electronic databases (PubMed, Embase, Cochrane, Scielo, Scielo Brazil, Virtual Health Library Regional Portal and Google Scholar) were systematically searched. The search was updated on 3 February 2020., Results: Infections (relative risk (RR): 3.26, 95% confidence interval (CI): 1.5-6.7, p = .001), history of serositis (RR: 2.59, 95% CI: 1.31-5.11, p = .006) and anti-RNP positivity (RR: 3.08, 95% CI: 1.39-6.78, p = .005) were associated risk factors for PROM, while anti-RNP positivity (RR: 3.37, 95% CI: 1.35-8.40; p = .009) were associated with premature PROM (PPROM). The prevalence of PROM and PPROM was 28.7% and 12.9%, respectively. In the systematic review, the prevalence of PROM and PPROM was 2.7%-35% (I 2 = 87.62%) and 2.8%-20% (I 2 = 79.56%), respectively., Conclusions: PROM, both at term and preterm, occurs more frequently in women with lupus than in the general population. A history of serositis, anti-RN, infections and immunosuppression during pregnancy may increase the susceptibility to PROM. The systematic review did not find any study with the main objective of evaluating PROM/PPROM in women with lupus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease affecting both adults and children. Belimumab is the only biologic approved for SLE, and the first in a class of drugs known as B-lymphocyte stimulator-specific inhibitors. The introduction of intravenous belimumab in 2011 was a major advance, being the first new therapy approved for SLE in over 50 years. As of April 2021, more than 7200 people with SLE have received belimumab in clinical studies, and it is approved in over 75 countries for the treatment of adults with SLE. A subcutaneous, self-injectable belimumab formulation was licensed in 2017 by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Belimumab was then approved for use in children in Europe, the USA and Japan in 2019, and China and Brazil in 2020. Recently, belimumab became the first FDA-approved drug for the treatment of adults with active lupus nephritis (LN), the most-common severe manifestation of SLE.Over the past 10 years, belimumab has established its position as a disease modifier in the SLE treatment paradigms. Robust evidence from randomised clinical studies and observational, real-world studies has demonstrated the tolerability and efficacy of belimumab for reducing disease activity and the risk of new, severe SLE flares. This enables patients to taper their glucocorticoid use, which limits damage accumulation. Significantly more patients with active LN met the criteria for renal responses and were at less risk of a renal-related event or death after receiving belimumab plus standard therapy, compared with standard therapy on top of mandatory steroid reduction. Ongoing clinical studies are evaluating belimumab's effectiveness in various indications beyond SLE. Post-marketing and registry studies are gathering additional data on key areas such as pregnancy outcomes after belimumab exposure and belimumab co-administration with other biologics.

Objective: The objective of this study was to evaluate the potential impact of irreversible damage accrual in women with systemic lupus erythematosus (SLE) and adverse maternal and/or fetal/neonatal outcomes., Methods: Retrospective cohort study with SLE pregnant patients was carried out from January 2011 to January 2020 at the Hospital University Pedro Ernesto (HUPE) of the State University of Rio de Janeiro, Brazil. Irreversible damage was defined according to SLICC/ACR damage index (SDI). The association of SDI on pregnancy outcomes was established by univariate and multivariate regression models and included demographic and clinical variables., Results: This study included data from 260 patients in their first pregnancies after SLE diagnosis, with a quarter of them (67/260) scoring one or more points on SDI at the beginning of prenatal care. These patients presented more frequently adverse maternal events, namely, disease activity during pregnancy ( p = 0.004) and puerperium ( p = 0.001), active lupus nephritis ( p = 0.04), and hospitalizations ( p = 0.004), than those with no SDI score. Similarly, the risks of adverse fetal and neonatal outcomes were also higher among the patients with SDI ≥ 1 (59.7% vs 38.3% p = 0.001) even after controlling data for disease activity (SLEPDAI > 4). Patients with SDI ≥ 1 presented more frequently preterm deliveries (46.3% vs 31.6%; p = 0.01), small for gestational age infants (28.3% vs 18.1%; p = 0.04), and neonatal intensive care unit admission (26.9% vs 1.5%; p < 0.001). The multivariate analyses showed that SDI ≥ 1 is an independent risk factor for hospitalization due to obstetric complications ( p = 0.0008) and preterm delivery ( p = 0.009)., Conclusion: Pregnant SLE patients who present irreversible damage accrual may have higher risk of maternal and fetal adverse outcomes, independently of disease activity. These results should be validated in further prospective studies.

The objectives of the 16th International Congress on Antiphospholipid Antibodies (aPL) Task Force on Clinical Manifestations of Antiphospholipid Syndrome (APS) were to critically analyze: a) the definition of "APS"; b) the current knowledge on non-traditional manifestations associated with aPL; and c) the risk stratification strategies in aPL-positive patients. The quality of evidence was assessed by the GRADE system. The task force concluded that: a) APS does not have a uniform definition given the heterogeneity of the clinical presentations and different aPL profiles; b) current literature supports the role for aPL testing in cases of thrombocytopenia and recurrent cardiac events but are limited by vast heterogeneity, providing an overall low-to-very low level of evidence; and c) risk stratification strategies in aPL-positive patients, such as aPL-Score and Global APS Score, can be useful in clinical practice. International multicenter studies are still highly needed to improve the quality of available evidence and consequently the strength of future recommendations.

Objective: There is a broad spectrum of eye involvement in antiphospholipid syndrome (APS). The majority of descriptions are presented as case reports that include mostly APS patients secondary to systemic lupus erythematosus (SLE), with no compelling evidence in primary APS (PAPS). This study aimed to describe ocular manifestations in our well-defined PAPS cohort (APS-Rio) and then perform a systematic literature review (SLR) of ocular manifestations in patients with APS or positivity to aPL without SLE., Methods: We retrospectively analyzed PAPS patients followed at our outpatient clinics. All patients fulfilled Sydney APS classification criteria (2006). We evaluated them for ocular symptoms and previous ocular diagnoses. Antiphospholipid antibodies and clinical APS manifestations were compared between patients with and without ocular manifestations. For the SLR, electronic databases were searched up to November 2019., Results: We studied 105 PAPS patients; 90.5% were female and 56.2% were Caucasian. We found ocular manifestations in 37.1% of our cohort. Thrombosis was the main criteria manifestation (95.2%) and lupus anticoagulant was the most prevalent antibody. Ophthalmologic diagnoses were present in 7 patients, with 5 having retinal vessels thromboses. Amaurosis fugax was the leading complaint, present in 30 patients. In the univariate analysis, amaurosis fugax was related to livedo (p = 0.005), Raynaud's phenomenon (p = 0.048) and the presence of anticardiolipin antibody (≥40 GPL/MPL) (p = 0.041). Hemianopia was associated with arterial hypertension (p = 0.049). In the multivariate analysis, the only association found was between livedo and amaurosis fugax (OR 4.09, 95%CI 1.5-11.11, p = 0.006). Our SLR incorporated 96 articles of ocular manifestations in patients with PAPS or positivity to aPL without SLE. Ocular findings varied from 5 to 88%, including anterior and posterior segments, orbital and neuro-ophthalmologic changes., Conclusion: There is little evidence on ocular manifestations in PAPS. We described an association between livedo and amaurosis fugax. Prospective studies are needed to promote the best treatment and avoid blindness in PAPS patients.

Objective: The understanding of systemic lupus erythematosus (SLE) and lupus nephritis (LN) pathogenesis remains incomplete. This review assessed LN development in SLE, within-LN progression and progression to end-stage renal disease (ESRD)., Methods: A keyword-based literature search was conducted, and 26 publications were included., Results: Overall, 7-31% of patients had LN at SLE diagnosis; 31-48% developed LN after SLE diagnosis, most within 5 years. Class IV was the most commonly found LN class and had the worst prognosis. Histological transformation occurred in 40-76% of patients, more frequently from non-proliferative rather than proliferative lesions. Cumulative 5- and 10-year ESRD incidences in patients with SLE were 3% and 4%, respectively, and 3-11% and 6-19%, respectively, in patients with SLE and LN., Conclusions: Elevated serum creatinine was identified as a predictor of worsening disease state, and progression within LN classes and from SLE/LN to ESRD. This review highlights the substantial risk for developing LN and progressing to ESRD amongst patients with SLE.

Objective: To analyze the impact of different classes of lupus nephritis as risk variables for maternal and fetal adverse outcomes in a cohort of pregnant lupus patients., Methods: This is a cohort study with retrospective and prospective data collection, conducted at the University Hospital of State University of Rio de Janeiro, Brazil, from 2011 to 2016. A total of 147 pregnancies of 137 systemic lupus erythematosus patients of whom 66 had lupus nephritis were included. Demographic and clinical features, as well as maternal and fetal outcomes were observed for each nephritis histological class among systemic lupus erythematosus patients and compared with those without nephritis. Categorical variables were expressed as absolute and relative frequencies and numerical variables as means and standard deviation. The chi-square test with Fisher's correction and Student's t-test were used for statistical analysis. A pvalue < 0.05 was considered statistically significant., Results: Systemic lupus erythematosus patients with proliferative nephritis (classes III/IV, n = 54) presented more frequent disease flares ( p = 0.02), continuous active disease during pregnancy and puerperium ( p = 0.006), hospitalization due to systemic lupus erythematosus ( p < 0.001), hospitalization not directly associated to systemic lupus erythematosus ( p = 0.04), higher frequency of cesarean delivery ( p = 0.03) and preeclampsia ( p = 0.01) than patients without nephritis. Permanent damage measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was more frequent in classes III/IV than among the other patients. The frequency of adverse fetal outcomes such as prematurity and admission to neonatal intensive care unit were not different among systemic lupus erythematosus patients with or without nephritis. However, perinatal deaths were more frequent in patients with all classes of nephritis ( p = 0.003)., Conclusion: Systemic lupus erythematosus patients with proliferative nephritis (classes III/IV) have a higher frequency of adverse maternal outcomes. This is probably due to the major impact of proliferative forms of nephritis on women's global heath, which is corroborated by the higher Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index findings, although we cannot exclude the negative influence of disease activity for the maternal adverse events. The findings indicate a need for further lupus nephritis classification beyond the nonspecific term nephritis in the context of lupus pregnancy as the impact on maternal and fetal outcomes varies according to histological class.

This study analyzed maternal and fetal outcomes of pregnancies of neuropsychiatric systemic lupus erythematosus patients followed in a reference unit. This retrospective cohort study included 26 pregnancies of patients seen between 2011 and 2015 included with history and/or active neuropsychiatric systemic lupus erythematosus among 135 pregnancies. Three patients had active neuropsychiatric systemic lupus erythematosus at conception, but only one remained with neurological activity during gestation, characteristically related to the inadvertent suspension of medications. Twenty six percent of the newborns were small for gestational age and 40% of live births were premature, with no neonatal death or early complications of prematurity. Preeclampsia was diagnosed in nine pregnancies, with two cases of early severe form that resulted in intrauterine fetal death. Patients with neuropsychiatric systemic lupus erythematosus had more prematurity and preeclampsia compared to patients without neuropsychiatric disease. However, when concomitant lupus nephritis was excluded, the gestational results of neuropsychiatric systemic lupus erythematosus patients were more favorable.

Antiphospholipid Syndrome (APS) is an autoimmune disease characterized by recurrent thromboses and fetal losses with the presence of antiphospholipid antibodies. The main treatment to prevent recurrent thrombotic events is oral anticoagulation with vitamin K antagonist (VKA), which requires frequent monitoring and dosage adjustments. Outpatient anticoagulation monitoring has its limitations, such as patients spending long hours between the testing procedure and waiting for the results to be adjusted. To optimize this adjustment and to improve APS patients-doctors relationship, we developed a website to help monitor APS patients, called Antiphospholipid Syndrome On Cloud or APSOnCloud. To test it, since March 2014 to March 2016, we registered 20 patients with APS that have inserted 132 international normalized ratio (INR) values. Sixty two percent were out of range and it took on average 7 hours for the doctor in charge to adjust these values. The mean time in therapeutic range was 58.1%. Our preliminary experience in monitoring VKA oral anticoagulation on APSOnCloud suggests that patients with APS might benefit from this web-based monitoring.

Diagnostic strategy studies commonly focus on the accuracy of tests in diagnosing, and grading this body of evidence is a challenge in itself because (1) standard tools for grading evidence were designed for questions about treatment rather than diagnostic testing; and (2) the clinical usefulness of a diagnostic strategy depends on multiple links in a chain of evidence connecting the performance of a test to changes in clinical outcomes. The application of the GRADE approach requires a shift in clinicians' thinking to clearly recognize that, whatever their accuracy, diagnostic tests are valuable only if they result in improved outcomes for patients., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Safety data were pooled and analyzed from one phase 2 and two phase 3 double-blind, placebo-controlled, repeat-dose systemic lupus erythematosus (SLE) trials of belimumab 1, 4 (phase 2 only), and 10 mg/kg. Types and rates of adverse events (AEs) were similar across treatment groups. Rates of patients experiencing any serious AE were 16.6%, 19.5%, 13.5%, and 18.0% with placebo, and belimumab 1, 4, and 10 mg/kg, respectively; rates of serious infusion reactions (including hypersensitivity reactions) occurring on the same days as infusions were 0.4%, 0.9%, 0%, and 0.9%, and rates of serious infections were 5.5%, 7.1%, 6.3%, and 5.3%. Malignancy rates/100 patient-years (excluding non-melanoma skin cancer) were 0.29 with placebo vs. 0.20 with all belimumab doses combined; mortality rates/100 patient-years were 0.43 vs. 0.73. These data support the conclusion that belimumab in combination with standard SLE therapy was generally well tolerated in a predominantly autoantibody-positive population with active SLE.

Antiphospholipid Syndrome (APS) has been widely recognized as a risk factor for the recurrence of both thrombosis and pregnancy losses; however the optimal treatment of patients is debatable. The aim of this paper was to establish a consensus among experts on the treatment of APS in pregnancy. A questionnaire that described possible different clinical situations was sent to the International Advisory Board of the 10th International Congress on Antiphospholipid Antibodies. Sixteen experts from different medical branches and different geographic areas sent their replies. The consensus was that treatment for APS pregnant patients should be low molecular weight heparin (LMWH) and low dose aspirin (LDA). The dosage, and frequency of LMWH depends on different situations, including the body weight and past history. Patients with previous thromboses usually receive two injections per day. Warfarin can also be used from 14 to 34 weeks, for patients with previous stroke or severe arterial thromboses. The use of intravenous immunoglobulin (IVIG) seems to be restricted to patients with pregnancy losses despite conventional treatment. The experts usually advised barrier methods of contraception, intrauterine device (if the patient is not taking corticosteroids) or progestins. Oral contraception with oestrogens was usually avoided.

We conducted a randomized, controlled study to assess the need for hydroxychloroquine (HCQ) during lupus pregnancy and to assess safety. Twenty consecutive pregnant patients with similar characteristics were enrolled. The HCQ group included eight patients with systemic lupus erythematosus (SLE) and two with discoid lupus erythematosus (DLE). The placebo (PL) group included nine patients with SLE and one with DLE. The HCQ group had no flare-ups. SLEPDAI scores were similar at study entry, and at conclusion the placebo group had significantly higher scores. One patient had improvement of skin lesions and another of arthritis, allowing a decrease of prednisone dose. There were no retinal effects. Three patients in the PL group flared up, two with skin rashes, one also with arthritis and uveitis, and one (previously in remission on HCQ) with hemolytic anemia, polyserositis and anti-dsDNA antibody. Toxemia was diagnosed in only three patients in the PL group (one fetal death). Comparing prednisone dosage change, we noted a decrease in the HCQ and an increase in the PL group. Delivery age and Apgar scores were higher in the HCQ group. Neonatal examination did not reveal congenital abnormalities, nor did a neuro-ophthalmological and auditory evaluation at 1.5-3 y of age. In spite of the small number of patients studied, we noted beneficial effects of HCQ during lupus pregnancy, as measured by SLEPDAI and decrease in prednisone dose with no detriment to patients' health.

Six unusual tumours of the skull and skull base are illustrated in this pictorial essay; for three of the tumours, both magnetic resonance imaging and computed tomography were performed preoperatively. These two imaging modalities can provide complementary information in the preoperative evaluation of unusual tumours of the skull and skull base.