Therapeutic Strategies and Outcomes in Neuropsychiatric Systemic Lupus Erythematosus: An International Multicenter Retrospective Study.

OBJECTIVES: The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptom severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. METHODS: This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. RESULTS: The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, p= 0.04). Age at diagnosis and focal central events emerged as additional response predictors. CONCLUSION: NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

Microstructural Changes in the Corpus Callosum in Systemic Lupus Erythematous.

Central nervous system (CNS) involvement in childhood-onset systemic lupus erythematosus (cSLE) occurs in more than 50% of patients. Structural magnetic resonance imaging (MRI) has identified global cerebral atrophy, as well as the involvement of the corpus callosum and hippocampus, which is associated with cognitive impairment. In this cross-sectional study we included 71 cSLE (mean age 24.7 years (SD 4.6) patients and a disease duration of 11.8 years (SD 4.8) and two control groups: (1) 49 adult-onset SLE (aSLE) patients (mean age of 33.2 (SD 3.7) with a similar disease duration and (2) 58 healthy control patients (mean age of 29.9 years (DP 4.1)) of a similar age. All of the individuals were evaluated on the day of the MRI scan (Phillips 3T scanner). We reviewed medical charts to obtain the clinical and immunological features and treatment history of the SLE patients. Segmentation of the corpus callosum was performed through an automated segmentation method. Patients with cSLE had a similar mid-sagittal area of the corpus callosum in comparison to the aSLE patients. When compared to the control groups, cSLE and aSLE had a significant reduction in the mid-sagittal area in the posterior region of the corpus callosum. We observed significantly lower FA values and significantly higher MD, RD, and AD values in the total area of the corpus callosum and in the parcels B, C, D, and E in cSLE patients when compared to the aSLE patients. Low complement, the presence of anticardiolipin antibodies, and cognitive impairment were associated with microstructural changes. In conclusion, we observed greater microstructural changes in the corpus callosum in adults with cSLE when compared to those with aSLE. Longitudinal studies are necessary to follow these changes, however they may explain the worse cognitive function and disability observed in adults with cSLE when compared to aSLE.

Cognitive Performance in Patients with Systemic Lupus Erythematosus Using the Ped-ANAM.

Computerized batteries have been widely used to investigate cognitive impairment (CI) in patients with SLE. The aim of this study was to evaluate the cognitive performance of patients with SLE in relation to healthy controls using the Pediatric Automated Neuropsychological Assessment Metrics (Ped-ANAM) battery. In addition, we aimed to examine differences in Ped-ANAM scores according to age of disease onset, presence of disease activity, and disease damage. We included 201 consecutive adult-onset (aSLE) and childhood-onset SLE (cSLE) patients who were being followed at the hospital's rheumatology outpatient clinic and 177 healthy controls. We applied the percentage of correct answers on the Ped-ANAM subtests and the Performance Validity Index (PVI) metric and correlated them with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus Erythematosus Damage Index (SDI). Then, we established their relationships with neuropsychiatric systemic lupus erythematosus (NPSLE). We observed CI in a total of 38 (18.9%) SLE patients and 8 (4.5%) healthy controls (p < 0.001). CI was observed in eight (19.5%) cSLE patients and 32 (20%) aSLE patients (p = 0.8175). Individual analysis of the aSLE subtests showed a significant difference in all subtests compared to healthy controls; the greatest differences were in matching to sample (p < 0.001) and memory search ( p < 0.001). In the cSLE group, we observed a difference in the code substitution subtests (p = 0.0065) compared to the healthy controls. In the evaluation of clinical outcomes, disease activity was significantly correlated with CI in cSLE (r = 0.33; p = 0.042) and aSLE (r = 0.40; p = 0.001). We also observed an association between disease activity and neuropsychiatric manifestations (p = 0.0012) in aSLE. In conclusion, we determined that cognitive dysfunction, mainly in memory and attention, was more prevalent in patients with SLE. In both the cSLE and aSLE groups, disease activity was associated with worse cognitive function. This is the first study to use the Ped-ANAM in Brazil. Longitudinal studies are necessary to determine how the Ped-ANAM will perform over time.

Longitudinal comparison of IL-6, IL-10, and IL-12 cytokine profiles in adult and childhood-onset systemic lupus erythematosus.

Objective: To compare the levels of Th1 (IL-12) and Th2 (IL-6 and IL10) cytokines over a two-year period among systemic lupus erythematosus patients with childhood-onset (cSLE), adult-onset (sSLE), and healthy controls, and correlate with their clinical, laboratory, and treatment manifestations. Methods: The study included 63 patients with cSLE [57 (90%) women; mean age 19.7 ± 4.3 years (range = 10-29); mean disease duration 7.3 ± 4.2 years (range 2-15)], 67 patients with aSLE [65 (97%) women; mean age of 39.9 ± 11.8 years (range 21-68); disease duration 7.7 ± 3.1 years (range 4-16)], and 40 healthy controls [36 (90%) women; mean age of 29.6 ± 10 years (range 12-49)]. cSLE and aSLE patients were paired by disease duration. Clinical and laboratory manifestations, disease activity (SLEDAI), cumulative damage (SDI), and current drug exposures were evaluated. Symptoms of anxiety and depression were evaluated by the Beck inventory (BAI and BDI, respectively). Th1 (IL-12) and Th2 (IL-6 and IL-10) cytokines were measured by the ELISA test. Data were collected at four different time points (TI, TII, TIII, and TIV) and compared by non-parametric tests. Results: IL-6 levels were significantly higher in aSLE patients compared to healthy controls at times I, II, and III (TI p = 0.013, TII p = 0.015, TIII p = 0.004, and TIV p = 0.634). However, no difference was observed between cSLE patients and healthy controls (TI p = 0.223, TII p = 0.613, TIII p = 0.341, and TIV p = 0.977). In addition, no difference was observed between aSLE and cSLE patients (TI p = 0.377, TII p = 0.123, TIII p = 0.105, and TIV p = 0.591). The levels of IL-12 were significantly higher in cSLE patients compared to healthy controls at all time points (TI p = 0.04, TII p < 0.001, TIII p = 0.015, and TIV p = 0.021). aSLE patients showed significantly elevated levels when compared to healthy controls at time III and IV (TI p = 0.752, TII p = 0.827, TIII p = 0.011*, and TIV p < 0.001*). cSLE patients showed significantly higher levels than aSLE patients at times I and II (TI p = 0.07*, TII p < 0.001*, TIII p = 0.998, and TIV p = 0.140). In aSLE patients, IL-6 was associated with headache (p = 0.006), arthritis (p = 0.044), and nephritis (p = 0.012); IL-10 was associated with nephritis (p = 0.043), hypocomplementemia (p = 0.001), and disease activity (p = 0.001); in these patients, IL-12 was associated with alopecia (p = 0.025) and leukopenia (p = 0.044). In cSLE patients, IL-6 was associated with arthritis (p = 0.022) and malar rash (p = 0.012). Conclusion: aSLE and cSLE patients with long disease duration present similar levels of cytokines, despite differences in clinical activity patterns over time.

Factors associated with neuropsychiatric involvement in Latin American patients with systemic lupus erythematosus.

INTRODUCTION: Factors related to presentation of neuropsychiatric (NP) SLE manifestations, early in the course of the disease, and during follow up have not been clearly established. PURPOSE: To identify disease and non-disease related factors associated with NP manifestations in early SLE. METHODS: We included 1193 patients from the GLADEL inception cohort free of NP involvement at cohort entry. We evaluated the association of demographic, clinical and laboratory data with NP involvement during follow-up. STATISTICAL METHODS: Independent factors associated with NP involvement were identified using a multivariable Cox regression model. RESULTS: Factors independently associated with NP manifestations were: mestizo ethnicity (HR 1.701, 95% CI 1.282-2.258, p = 0.0002), myalgias/myositis (HR 1.832, 95% CI 1.335-2.515, p = 0.0002), pneumonitis (HR 2.476, 95% CI 1.085-5.648, p = 0.0312), shrinking lung (HR 2.428, 95% CI 1.074-5.493, p = 0.0331) and hemolytic anemia (HR 1.629, 95% CI 1.130-2.347, p = 0.0089). Longer disease duration at cohort entry (13 to 24 months) was associated with a lower risk of developing NP manifestations (HR 0.642, 95% CI 0.441-0.934, p = 0.0206). CONCLUSIONS: Patients with myalgias/myositis, pneumonitis, shrinking lung and hemolytic anemia are at higher risk of NP involvement, whereas longer disease duration at cohort entry is associated with a lower risk of developing NP involvement.

Gastrointestinal involvement in systemic lupus erythematosus: A systematic review.

INTRODUCTION: Gastrointestinal involvement is a common complain observed in 40-60% of systemic lupus erythematosus (SLE) patients. We performed a systematic review of clinically severe and potential life-threatening gastrointestinal manifestations and discuss clinical presentation, pathogenesis and treatment. METHODS: We performed a literature search in English literature using PubMed and Embase from 2000 to December 2020. The following MeSH terms: systemic lupus erythematosus, protein-losing enteropathy, ascites, pancreatitis, vasculitis, intestinal vasculitis, enteritis and diarrhea published in the English literature. RESULTS: We identified 141 studies (case reports, case series and cohort studies). The most frequent presenting symptoms are acute abdominal pain, nausea, and vomiting. Many of the manifestations were associated with disease activity. Histological features are rarely available, but both vasculitis and thrombosis have been described. There is no treatment guideline. The majority of patients were treated with corticosteroids and the most common immunososupressant were azathioprine, cyclophosphamide and mycophenolate. CONCLUSION: Vasculitis and thrombosis may be responsible for severe life-threatening manifestations such as pancreatitis, protein loosing gastroenteritis, acalculous cholecistyitis and enteritis.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with systemic lupus erythematosus.

BACKGROUND: Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is an uncommon subtype of peripheral neuropathy (PN) and especially when associated with systemic lupus erythematosus (SLE). There are few reports characterizing PN-associated to SLE, in particular CIDP. This study reviewed the frequency and profile of SLE-related CIDP in our cohort and in the literature and propose a treatment scheme for CIDP associated with SLE. METHOD: We reviewed our database to identify patients with CIDP and SLE. The literature was also reviewed following the guidelines of PRISMA and using the terms "Polyradiculoneuropathy", "Chronic inflammatory demyelinating polyradiculoneuropathy", "CIDP", "Systemic lupus erythematosus", "SLE", "Autoimmune diseases of the nervous system" until December 2019. Selected articles were published in English. RESULTS: We identified 3 patients with SLE and CIDP in our cohort of 1,349 patients with SLE (0.2%). All patients were female, aged between 30 and 44 years and 2 (66.7%) had active disease in other organs. In the literature, we identified additional 16 patients. A predominance of women with disease activity, specially nephritis and hematological involvement, was observed. Treatment schemes are diverse, including corticosteroids and immunosuppressive drugs. CONCLUSION: Although rare, CIDP has increased frequency in SLE. Women and younger age should rise suspicion of an underlying autoimmune disease. We suggest that CIDP should be included as a possible neuropsychiatric manifestation in SLE.

Correction to: Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score.

An amendment to this paper has been published and can be accessed via the original article.

Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score.

BACKGROUND: Human herpesviruses (HHVs) are responsible for a significant number of clinical manifestations in systemic lupus erythematous (SLE) patients. The aim of this study was to determine the frequency of active HHV infections in SLE patients and correlating them with disease activity. METHODS: Serum samples were collected from 71 SLE patients and their DNAs were extracted and analyzed to detect HHV-DNA viruses using the nucleic acid amplification technique. RESULTS: Fifteen out of the 71 (21.1%) patients tested positive for the HHV-DNA virus. Of them, 11/15 HHV-DNA-positive patients (73.3%) had SLE activity index (SLEDAI - Systemic Lupus Erythematosus Disease Activity Index) ≥8 (p = 0.0001). Active HCMV infection was the mostly frequently observed infection, occurring in 6/15 patients (40%). The frequencies of other active viral infections were 22% for HSV-1, 16.7% for HHV-7, and 5.5% for HSV-2. Viral coinfection (two or more viruses detected in the same sample) occurred in three patients (16.7%). Active HHV infections in SLE patients are more frequent in those with active SLE (≥8), who is at high risk of HHV reactivation and HCMV disease. CONCLUSION: Viral surveillance is important to identify active HHV infections that can cause clinical symptoms and other complication in SLE patients.

Clinical features, damage accrual, and survival in patients with familial systemic lupus erythematosus: data from a multi-ethnic, multinational Latin American lupus cohort.

OBJECTIVES: This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. RESULTS: A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08-3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00-2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14-0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30-1.55) or mortality (HR = 1.23; 95% CI 0.26-4.81). CONCLUSION: Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.

Familial Aggregation of Childhood- and Adulthood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: To assess the familial occurrence of systemic lupus erythematosus (SLE) in a large Brazilian cohort. METHODS: Consecutive patients with SLE were recruited and stratified according to age at disease onset into childhood-onset SLE or adult-onset SLE. Each patient was personally interviewed regarding the history of SLE across 3 generations (first-, second-, and third-degree relatives). Recurrence rates were analyzed for each degree of relation. RESULTS: We included 392 patients with SLE (112 with childhood-onset SLE and 280 with adult-onset SLE). We identified 2,574 first-degree relatives, 5,490 second-degree relatives, and 6,805 third-degree relatives. In the combined overall SLE cohort, we observed a familial SLE recurrence rate of 19.4 in first-degree relatives, 5.4 in second-degree relatives, and 3.0 in third-degree relatives. Recurrence rates were higher for first- and second-degree relatives of patients with childhood-onset SLE than for first- and second-degree relatives of patients with adult-onset SLE (25.2 versus 18.4 for first-degree, and 8.5 versus 4.5 for second-degree), while in third-degree relatives, recurrence rates were higher in adult-onset SLE than in childhood-onset SLE (P = 2.2 × 10-4 for differences in recurrence proportions between childhood-onset SLE and adult-onset SLE). There were no phenotypic differences in patients from multicase versus single-case families, and there was no sex-skewing observed in the offspring of patients with SLE. CONCLUSION: The greater decline in SLE recurrence rate by generation in childhood-onset SLE versus adult-onset SLE suggests a more polygenic and epistatic inheritance and suggests that adult-onset SLE may be characterized by fewer risk factors that are individually stronger. This finding suggests a higher genetic load in childhood-onset SLE versus adult-onset SLE and a difference in the genetic architecture of the disease based on age at onset.

Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score

Abstract Background: Human herpesviruses (HHVs) are responsible for a significant number of clinical manifestations in systemic lupus erythematous (SLE) patients. The aim of this study was to determine the frequency of active HHV infections in SLE patients and correlating them with disease activity. Methods: Serum samples were collected from 71 SLE patients and their DNAs were extracted and analyzed to detect HHV-DNA viruses using the nucleic acid amplification technique. Results: Fifteen out of the 71 (21.1%) patients tested positive for the HHV-DNA virus. Of them, 11/15 HHV-DNA-positive patients (73.3%) had SLE activity index (SLEDAI - Systemic Lupus Erythematosus Disease Activity Index) ≥8 (p = 0.0001). Active HCMV infection was the mostly frequently observed infection, occurring in 6/15 patients (40%). The frequencies of other active viral infections were 22% for HSV-1, 16.7% for HHV-7, and 5.5% for HSV-2. Viral coinfection (two or more viruses detected in the same sample) occurred in three patients (16.7%). Active HHV infections in SLE patients are more frequent in those with active SLE (≥8), who is at high risk of HHV reactivation and HCMV disease. Conclusion: Viral surveillance is important to identify active HHV infections that can cause clinical symptoms and other complication in SLE patients.

Disease activity and thromboembolic events in women with systemic lupus erythematosus with and without anti-phospholipid syndrome: users of the 52-mg levonorgestrel-releasing intrauterine system.

PURPOSE: The disease status and thromboembolic events in women with systemic lupus erythematosus (SLE), with and without anti-phospholipid syndrome (APS), were evaluated before and after placement of the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: A retrospective cohort study, with review of medical records of SLE women, who received an LNG-IUS placement between January 2007 and December 2016, carried out at the University of Campinas Medical School, Brazil. The outcomes included the disease activity (SLEDAI-2K) and damage index scores (SLICC/ACR-DI) presented for each year of device use, as well as venous/arterial thrombotic events, insertion up to a median of 5 years. The author's used χ2, Fisher's exact and the Mann-Whitney tests for analysis and generalized estimating equations for score comparison. RESULTS: The study evaluated 46 women with SLE, 18 with and 28 without APS; the mean age (± standard deviation [SD]) was 31.8 (SD ± 8.3) years old. The length of follow-up after LNG-IUS placement was 5.6 (SD ± 2.7) and 4.1 (SD ± 2.3) years for the groups with and without APS, respectively. Comparison of the groups found that the SLEDAI and SLICC mean scores were low for both at baseline, without variations through the follow-up. After LNG-IUS placement, two women presented three thrombotic arterial events, and one of them died from causes unrelated to LNG-IUS use. CONCLUSIONS: Our results, although restricted, provide information to policymakers and health professionals that the use of a 52 mg LNG-IUS over a 5-year median did not increase disease activity or damage index scores among women with SLE, with and without APS.

Predictors of Remission and Low Disease Activity State in Systemic Lupus Erythematosus: Data from a Multiethnic, Multinational Latin American Cohort.

OBJECTIVE: To determine the predictors of remission and low disease activity state (LDAS) in patients with systemic lupus erythematosus (SLE). METHODS: Three disease activity states were defined: Remission = SLE Disease Activity Index (SLEDAI) = 0 and prednisone ≤ 5 mg/day and/or immunosuppressants (maintenance dose); LDAS = SLEDAI ≤ 4, prednisone ≤ 7.5 mg/day and/or immunosuppressants (maintenance dose); and non-optimally controlled state = SLEDAI > 4 and/or prednisone > 7.5 mg/day and/or immunosuppressants (induction dose). Antimalarials were allowed in all groups. Patients with at least 2 SLEDAI reported and not optimally controlled at entry were included in these analyses. Outcomes were remission and LDAS. Multivariable Cox regression models (stepwise selection procedure) were performed for remission and for LDAS. RESULTS: Of 1480 patients, 902 were non-optimally controlled at entry; among them, 196 patients achieved remission (21.7%) and 314 achieved LDAS (34.8%). Variables predictive of a higher probability of remission were the absence of mucocutaneous manifestations (HR 1.571, 95% CI 1.064-2.320), absence of renal involvement (HR 1.487, 95% CI 1.067-2.073), and absence of hematologic involvement (HR 1.354, 95% CI 1.005-1.825); the use of immunosuppressive drugs before the baseline visit (HR 1.468, 95% CI 1.025-2.105); and a lower SLEDAI score at entry (HR 1.028, 95% CI 1.006-1.051 per 1-unit decrease). These variables were predictive of LDAS: older age at entry, per 5-year increase (HR 1.050, 95% CI 1.004-1.098); absence of mucocutaneous manifestations (HR 1.401, 95% CI 1.016-1.930) and renal involvement (HR 1.344, 95% CI 1.049-1.721); and lower SLEDAI score at entry (HR 1.025, 95% CI 1.009-1.042). CONCLUSION: Absence of mucocutaneous, renal, and hematologic involvement, use of immunosuppressive drugs, and lower disease activity early in the course of the disease were predictive of remission in patients with SLE; older age was predictive of LDAS.

Epidemiology, characterization, and diagnosis of neuropsychiatric events in systemic lupus erythematosus.

INTRODUCTION: Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a heterogeneity of clinical manifestations. The absence of diagnostic criteria and the lack of clinical trials is a challenge in clinical practice. Areas covered: A literature review was performed to describe epidemiology, characterization (clinical, immunological, and imaging), diagnosis and treatment of NPSLE. Classification criteria have been the first step towards a uniform definition. More recently, different attribution models have been developed to help to determine if the NP event is due to SLE. Disease activity is a major risk factor for NP events. Cytokines and autoantibodies are associated with NP events, however, only a few studies have identified risk factors for individual NP events. Expert opinion: Further research needs to search for and validate biomarkers for NPSLE and individual NP events, including neuroimaging findings, attribution models, and serologic markers. This will be a fundamental step in planning randomized control trials in the treatment of NPSLE to improve outcome.

Systemic Lupus Erythematosus and Pregnancy: A Single-Center Observational Study of 69 Pregnancies.

OBJECTIVE: To evaluate the effects of pregnancy in systemic lupus erythematosus (SLE) patients. METHODS: The present article is a retrospective cohort study. Data were collected from medical records of pregnant women with SLE from January 2002 to December 2012 at Universidade Estadual de Campinas, in the city of Campinas, state of São Paulo, Brazil. Systemic lupus erythematosus and disease activity were defined according to the American College of Rheumatology and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) criteria respectively. The means, standard deviations (SDs), percentages and correlations were performed using the SAS software, version 9.4 (SAS Institute Inc., Cary, NC, US). RESULTS: We obtained data from 69 pregnancies in 58 women. During pregnancy, a new flare was observed in 39.2% (n = 27). The manifestations were most common in patients with prior kidney disease, and mainly occurred during the third quarter and the puerperium. Renal activity occurred in 24.6% (n = 17), and serious activity, in 16% (n = 11). Of all deliveries, 75% (n = 48) were by cesarean section. Two maternal deaths occurred (3%). Preterm birth was the main complication in the newborns. The abortion rate was 8.7%. Severe SLEDAI during pregnancy was associated with prematurity (100%) and perinatal death (54%). CONCLUSION: The maternal-fetal outcome is worse in SLE when the women experience a flare during pregnancy. The best maternal-fetal outcomes occur when the disease is in remission for at least 6 months before the pregnancy.

OBJETIVO: Avaliar os efeitos da gravidez em pacientes com lúpus eritematoso sistêmico (LES). MéTODOS: Estudo de coorte retrospectivo. Os dados foram coletados de prontuários de mulheres com LES que engravidaram de janeiro de 2002 a dezembro de 2012 na Universidade Estadual de Campinas, São Paulo, Brasil. Lúpus eritematoso sistêmico e atividade da doença foram definidos segundo o American College of Rheumatology e os critérios do Índice de Atividade da Doença de Lúpus Eritematoso (SLEDAI, na sigla em inglês), respectivamente. As médias, os desvios-padrão (DP), as porcentagens e as correlações foram realizados utilizando o software SAS, versão 9.4 (SAS Institute Inc., Cary, NC, US). RESULTADOS: Obtivemos dados de 69 gestações em 58 mulheres. Durante a gravidez, a reatividade da doença foi observada em 39.2% (n = 27). As manifestações mais comuns foram em pacientes com doença renal prévia, e ocorreram principalmente no terceiro trimestre e no puerpério. Atividade renal ocorreu em 24,6% (n = 17), e atividade grave, em 16% (n = 11). De todos os partos, 75% (n = 48) foram por cesariana. Dois óbitos maternos ocorreram (3%). A prematuridade foi a principal complicação nos recém-nascidos. A taxa de aborto foi de 8,7%. O índice SLEDAI grave durante a gestação foi associado à prematuridade (100%) e à morte perinatal (54%). CONCLUSãO: O resultado materno-fetal é pior no LES quando as mulheres sofrem crise de reativação durante a gravidez. Os melhores desfechos materno-fetais ocorrem quando a doença está em remissão por pelo menos 6 meses anteriores à gestação.

Systemic lupus erythematosus and pregnancy: A single-center observational study of 69 pregnancies / Lúpus eritematoso sistêmico e gravidez: estudo observacional em um único centro com 69 gestações

Abstract Objective To evaluate the effects of pregnancy in systemic lupus erythematosus (SLE) patients. Methods The present article is a retrospective cohort study. Datawere collected from medical records of pregnant women with SLE from January 2002 to December 2012 at Universidade Estadual de Campinas, in the city of Campinas, state of São Paulo, Brazil. Systemic lupus erythematosus and disease activity were defined according to the American College of Rheumatology and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) criteria respectively. The means, standard deviations (SDs), percentages and correlations were performed using the SAS software, version 9.4 (SAS Institute Inc., Cary, NC, US). Results We obtained data from 69 pregnancies in 58 women. During pregnancy, a new flare was observed in 39.2% (n = 27). The manifestations were most common in patients with prior kidney disease, and mainly occurred during the third quarter and the puerperium. Renal activity occurred in 24.6% (n = 17), and serious activity, in 16% (n = 11). Of all deliveries, 75% (n = 48) were by cesarean section. Twomaternal deaths occurred (3%). Preterm birth was themain complication in the newborns. The abortion rate was 8.7%. Severe SLEDAI during pregnancy was associated with prematurity (100%) and perinatal death (54%). Conclusion Thematernal-fetal outcome is worse in SLE when thewomen experience a flare during pregnancy. The best maternal-fetal outcomes occur when the disease is in remission for at least 6 months before the pregnancy.

Resumo Objetivo Avaliar os efeitos da gravidez em pacientes com lúpus eritematoso sistêmico (LES). Métodos Estudo de coorte retrospectivo. Os dados foram coletados de prontuários de mulheres com LES que engravidaram de janeiro de 2002 a dezembro de 2012 na Universidade Estadual de Campinas, São Paulo, Brasil. Lúpus eritematoso sistêmico e atividade da doença foram definidos segundo o American College of Rheumatology e os critérios doÍndice deAtividadedaDoença de Lúpus Eritematoso (SLEDAI, nasigla eminglês), respectivamente. As médias, os desvios-padrão (DP), as porcentagens e as correlações foram realizados utilizando o software SAS, versão 9.4 (SAS Institute Inc., Cary, NC, US). Resultados Obtivemos dados de 69 gestações em58mulheres. Durante a gravidez, a reatividade da doença foi observada em 39.2% (n = 27). As manifestações mais comuns foram em pacientes com doença renal prévia, e ocorreram principalmente no terceiro trimestre e no puerpério. Atividade renal ocorreu em 24,6% (n = 17), e atividade grave, em 16% (n = 11). De todos os partos, 75% (n = 48) foram por cesariana. Dois óbitos maternos ocorreram (3%). A prematuridade foi a principal complicação nos recém-nascidos. A taxa de aborto foi de 8,7%. O índice SLEDAI grave durante a gestação foi associado à prematuridade (100%) e à morte perinatal (54%). Conclusão O resultado materno-fetal é pior no LES quando as mulheres sofrem crise de reativação durante a gravidez. Os melhores desfechos materno-fetais ocorrem quando a doença está em remissão por pelo menos 6 meses anteriores à gestação.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

Olfactory function in systemic lupus erythematosus and systemic sclerosis. A longitudinal study and review of the literature.

BACKGROUND/PURPOSE: To evaluate olfactory function in systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and healthy controls over a 2-year period, and to determine the association of olfactory dysfunction with age, disease activity, disease damage, treatment, anxiety and depression symptoms and limbic structures volumes. METHODS: Consecutive SLE and SSc patients were enrolled in this study. Clinical, laboratory disease activity and damage were assessed according to diseases specific guidelines. Olfactory functions were evaluated using the Sniffin' Sticks test (TDI). Volumetric magnetic resonance imaging (MRI) was obtained in a 3T Phillips scanner. Amygdalae and hippocampi volumes were analyzed using FreeSurfer® software. RESULTS: We included 143 SLE, 57 SSc and 166 healthy volunteers. Olfactory dysfunction was observed in 78 (54.5%) SLE, 35 (59.3%) SSc patients and in 24 (14.45%) controls (p<0.001) at study entry. SLE and SSc patients had significantly lower mean in all three phases (TDI) of the olfactory assessment when compared with healthy volunteers. In SLE, the presence of olfactory dysfunction was associated with older age, disease activity, higher anxiety and depression symptoms score, smaller left hippocampus volume, smaller left and right amygdalae volume and the presence of anti-ribosomal P (anti-P) antibodies. In SSc the presence of olfactory impairment was associated with older age, disease activity, smaller left and right hippocampi volumes and smaller right amygdala volume. Olfactory function was repeated after a 2-year period in 90 SLE, 35 SSc and 62 controls and was stable in all three groups. CONCLUSION: Both SLE and SSc patients with longstanding disease had significant reduction in all stages of TDI that maintained stable over a 2-year period. Olfactory dysfunction was associated with age, inflammation and hippocampi and amygdalae volumes. In SLE, additional association with anti-P, anxiety and depression symptoms was observed.