Search

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.

ObjectiveDescribe available data on birth defects and pregnancy loss in women with systemic lupus erythematosus (SLE) exposed to belimumab.MethodsData collected from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports up to 8 March 2020 were described. Belimumab exposure timing, concomitant medications and potential confounding factors were summarised descriptively.ResultsAmong 319 pregnancies with known outcomes (excluding elective terminations), 223 ended in live births from which birth defects were identified in 4/72 (5.6%) in belimumab-exposed pregnancies and 0/9 placebo-exposed pregnancies across 18 clinical trials, 10/46 (21.7%) belimumab-exposed pregnancies in the BPR prospective cohort (enrolled prior to pregnancy outcome) and 0/4 belimumab-exposed pregnancies in the BPR retrospective cohort (enrolled after pregnancy outcome), and 1/92 (1.1%) in belimumab-exposed pregnancies from postmarketing/spontaneous reports. There was no consistent pattern of birth defects across datasets. Out of pregnancies with known outcomes (excluding elective terminations), pregnancy loss occurred in 31.8% (35/110) of belimumab-exposed women and 43.8% (7/16) of placebo-exposed women in clinical trials; 4.2% (2/48) of women in the BPR prospective cohort and 50% (4/8) in the BPR retrospective cohort; and 31.4% (43/137) of belimumab-exposed women from postmarketing/spontaneous reports. All belimumab-exposed women in clinical trials and the BPR received concomitant medications and had confounding factors and/or missing data.ConclusionsObservations reported here add to limited data published on pregnancy outcomes following belimumab exposure. Low numbers of exposed pregnancies, presence of confounding factors/other biases, and incomplete information preclude informed recommendations regarding risk of birth defects and pregnancy loss with belimumab use.

Endothelial dysfunction is an initial stage of the atherogenic process, which can be evaluated by a noninvasive method (flow-mediated dilation - FMD) and has a well-established prognostic value for cardiovascular (CV) risk. Currently, there is no evidence of increased CV mortality in Behc¸et's disease (BD), although its association with endothelial dysfunction has been described. There are still doubts in the literature whether the presence of chronic vascular inflammation might trigger the development of atherosclerosis, despite BD remission, which is why this study was conducted.We analyzed 24 subjects in this cross-sectional study (12 patients with BD in remission and 12 subjects matched by gender age). Endothelial function was analyzed via FMD.The lowest median for FMD was presented by the BD group (2.025% - interquartile range (IQR) 7.785 versus 5.46% - IQR 3.625, P ¼ .18). The median total cholesterol in the BD group was lower than the controls (168 mg dL-1 - IQR 46 and 216.5 mg dL-1 - IQR 54, respectively, P ¼ .0193). In the right carotid artery, the intima-media thickness was equal to 0.740 - IQR 0.16 for the patients and 0.740 - IQR 0.11 for the controls (P ¼ .9473); on the left, 0.725 - IQR 0.13 and 0.745 - IQR 0.120 (P ¼ .4333), respectively.The lower median trend of FMD in patients with BD suggests endothelial dysfunction, despite clinical remission of the inflammatory disease, although our study is limited by the sample size and greater use of statins in BD group.

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as “unmet needs”, such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

Lupus is a complex disease that is often difficult to diagnose. Risks of diagnostic delays include non-specific signs and symptoms that mimic other diseases and a lack of diagnostic criteria and referral pathways for non-specialists. To address these issues, we convened a series of virtual meetings with members of our Addressing Lupus Pillars for Health Advancement clinical care team. Meeting participants included lupus physicians, treatment developers from biotechnology, patient advocacy group representatives from the Lupus Foundation of America and advocacy/government consultants. Causes and consequences of ambiguity in diagnosis and diagnostic delays were evaluated through historical, experiential and evidence-based accounts (survey data, literature reviews and patient testimonials). Discussions highlighted the need for a clearer understanding of the definition of lupus, the natural history of the disease and the need for advancements in biotechnology to support an accurate and timely diagnosis with the potential development of a lupus spectrum.

Disease modification has become a well-established concept in several therapeutic areas; however, no widely accepted definition of disease modification exists for SLE.We reviewed established definitions of disease modification in other conditions and identified a meaningful effect on ‘disease manifestations’ (ie, signs, symptoms and patient-reported outcomes) and on ‘disease outcomes’ (eg, long-term remission or progression of damage) as the key principles of disease modification, indicating a positive effect on the natural course of the disease. Based on these findings and the treatment goals and outcome measures for SLE, including lupus nephritis, we suggest a definition of disease modification based on disease activity indices and organ damage outcomes, with the latter as a key anchor. A set of evaluation criteria is also suggested.Establishing a definition of disease modification in SLE will clarify which treatments can be considered disease modifying, provide an opportunity to harmonise future clinical trial outcomes and enable comparison between therapies, all of which could ultimately help to improve patient outcomes. This publication seeks to catalyse further discussion and provide a framework to develop an accepted definition of disease modification in SLE.

Background/objective The epidemiology of vasculitis is variable in different geographic areas, and this issue has not been approached in Brazil yet. The objective of this study was to assess the frequency of vasculitis in specialized centers in Brazil. Methods This cross-sectional study was performed in 9 vasculitis outpatient clinics from 6 different states mainly from the Southeast and the Northeast regions of Brazil between 2015 and 2017. Diagnosis and/or classification criteria for Behcet disease (BD), Takayasu arteritis (TA), giant cell arteritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and cryoglobulinemic vasculitis (CryoVas) were used to include patients with at least 6 months of follow-up in this hospital-based survey. Results A total of 1233 patients with systemic vasculitis were included from the Southeast region. Behcet disease was the most frequent vasculitis (35.0%) followed by TA (26.4%), GPA (16.2%), PAN (5.8%), GCA (5.8%), EGPA (4.3%), MPA (3.4%), and CryoVas (3.0%). Up to 7.8% of vasculitis patients had a juvenile onset, and the frequency of vasculitides found in children and adolescents was as follows: TA (52.6%), BD (24.7%), GPA (12.4%), and PAN (10.3%). No cases of EGPA, MPA, and CryoVas were diagnosed before the age of 18 years. As a comparator, 103 vasculitis patients were included in the Northeast of Brazil where TA was found in 36.9% and BD in 31.1% of vasculitis cases. No GCA cases were found in the Northeast part of Brazil. Conclusions Similar to the epidemiology of vasculitis in Asia, BD and TA are the most frequent vasculitis in Southeastern Brazilian referral centers.

IntroductionLupus nephritis (LN) is more prevalent in patients with SLE of Asian ethnicity than in Caucasian patients. Belimumab became available in Japan in 2017 to treat patients with SLE, including those with LN. In the BLISS-LN trial (NCT01639339), belimumab showed a favourable effect on renal outcomes when combined with standard therapy (ST) starting at the induction treatment phase for active LN, but real-world effectiveness of belimumab in LN has not been extensively studied. Here we describe the protocol for the MOONLIGHT (post-Marketed effectiveness of belimumab cOhOrt and JapaN Lupus NatIonwide ReGistry (LUNA) coHorT) study, which will use data from a Japan postmarketing surveillance study and the Lupus Registry of Nationwide Institutions (LUNA) to evaluate the real-world effectiveness of belimumab plus ST versus ST alone in patients with a history of active LN who are not in the induction phase.Methods and analysisThis multicentre, retrospective, observational study (GSK Study 214710) will enrol adults with SLE and a history of active LN, holding ≥3 years of complete follow-up data from the initiation of belimumab (no continuous treatment required). Data for patients with belimumab plus ST treatment (postmarketing registry data, belimumab cohort) will be compared with those for patients with ST only treatment (LUNA data, comparison cohort). Patients who discontinue/initiate belimumab after the start of the follow-up may be included in the comparison/belimumab cohort, respectively. The primary endpoint will be the occurrence of renal flares, for which belimumab’s effectiveness will be estimated using a marginal structural model to consider time-dependent treatment and confounding factors. Secondary endpoints will include change in corticosteroid dose, renal disease activity, extrarenal disease activity, disease severity/activity biomarkers, LN class changes, end-stage kidney disease events and hospitalisations.Ethics and disseminationThis study will be conducted according to the Declaration of Helsinki and the local ethical guidelines. Findings will be submitted to peer-reviewed journals and presented at scientific meetings.

BACKGROUND Enrollment in pregnancy registries is challenging despite substantial awareness-raising activities, generally resulting in low recruitment owing to limited safety data. Understanding patient and physician awareness of and attitudes toward pregnancy registries is needed to facilitate enrollment. Crowdsourcing, in which services, ideas, or content are obtained by soliciting contributions from a large group of people using web-based platforms, has shown promise for improving patient engagement and obtaining patient insights. OBJECTIVE This study aimed to use web-based crowdsourcing platforms to evaluate Belimumab Pregnancy Registry (BPR) awareness among patients and physicians and to identify potential barriers to pregnancy registry enrollment with the BPR as a case study. METHODS We conducted 2 surveys using separate web-based crowdsourcing platforms: Amazon Mechanical Turk (a 14-question patient survey) and Sermo RealTime (a 11-question rheumatologist survey). Eligible patients were women, aged 18-55 years; diagnosed with systemic lupus erythematosus (SLE); and pregnant, recently pregnant (within 2 years), or planning pregnancy. Eligible rheumatologists had prescribed belimumab and treated pregnant women. Responses were descriptively analyzed. RESULTS Of 151 patient respondents over a 3-month period (n=88, 58.3% aged 26-35 years; n=149, 98.7% with mild or moderate SLE; and n=148, 98% from the United States), 51% (77/151) were currently or recently pregnant. Overall, 169 rheumatologists completed the survey within 48 hours, and 59.2% (100/169) were based in the United States. Belimumab exposure was reported by 41.7% (63/151) patients, whereas 51.7% (75/145) rheumatologists had prescribed belimumab to 10 patients who were pregnant or trying to conceive. Of the patients exposed to belimumab, 51% (32/63) were BPR-aware, and 45.5% (77/169) of the rheumatologists were BPR-aware. Overall, 60% (38/63) of patients reported belimumab discontinuation because of pregnancy or planned pregnancy. Among the 77 BPR-aware rheumatologists, 70 (91%) referred patients to the registry. Concerns among rheumatologists who did not prescribe belimumab during pregnancy included unknown pregnancy safety profile (119/169, 70.4%), and 61.5% (104/169) reported their patients’ concerns about the unknown pregnancy safety profile. Belimumab exposure during or recently after pregnancy or while trying to conceive was reported in patients with mild (6/64, 9%), moderate (22/85, 26%), or severe (1/2, 50%) SLE. Rheumatologists more commonly recommended belimumab for moderate (84/169, 49.7%) and severe (123/169, 72.8%) SLE than for mild SLE (36/169, 21.3%) for patients trying to conceive recently or currently pregnant. Overall, 81.6% (138/169) of the rheumatologists suggested a belimumab washout period before pregnancy of 0-30 days (44/138, 31.9%), 30-60 days (64/138, 46.4%), or >60 days (30/138, 21.7%). CONCLUSIONS In this case, crowdsourcing efficiently obtained patient and rheumatologist input, with some patients with SLE continuing to use belimumab during or while planning a pregnancy. There was moderate awareness of the BPR among patients and physicians.

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.

Background Enrollment in pregnancy registries is challenging despite substantial awareness-raising activities, generally resulting in low recruitment owing to limited safety data. Understanding patient and physician awareness of and attitudes toward pregnancy registries is needed to facilitate enrollment. Crowdsourcing, in which services, ideas, or content are obtained by soliciting contributions from a large group of people using web-based platforms, has shown promise for improving patient engagement and obtaining patient insights. Objective This study aimed to use web-based crowdsourcing platforms to evaluate Belimumab Pregnancy Registry (BPR) awareness among patients and physicians and to identify potential barriers to pregnancy registry enrollment with the BPR as a case study. Methods We conducted 2 surveys using separate web-based crowdsourcing platforms: Amazon Mechanical Turk (a 14-question patient survey) and Sermo RealTime (a 11-question rheumatologist survey). Eligible patients were women, aged 18-55 years; diagnosed with systemic lupus erythematosus (SLE); and pregnant, recently pregnant (within 2 years), or planning pregnancy. Eligible rheumatologists had prescribed belimumab and treated pregnant women. Responses were descriptively analyzed. Results Of 151 patient respondents over a 3-month period (n=88, 58.3% aged 26-35 years; n=149, 98.7% with mild or moderate SLE; and n=148, 98% from the United States), 51% (77/151) were currently or recently pregnant. Overall, 169 rheumatologists completed the survey within 48 hours, and 59.2% (100/169) were based in the United States. Belimumab exposure was reported by 41.7% (63/151) patients, whereas 51.7% (75/145) rheumatologists had prescribed belimumab to 10 patients who were pregnant or trying to conceive. Of the patients exposed to belimumab, 51% (32/63) were BPR-aware, and 45.5% (77/169) of the rheumatologists were BPR-aware. Overall, 60% (38/63) of patients reported belimumab discontinuation because of pregnancy or planned pregnancy. Among the 77 BPR-aware rheumatologists, 70 (91%) referred patients to the registry. Concerns among rheumatologists who did not prescribe belimumab during pregnancy included unknown pregnancy safety profile (119/169, 70.4%), and 61.5% (104/169) reported their patients’ concerns about the unknown pregnancy safety profile. Belimumab exposure during or recently after pregnancy or while trying to conceive was reported in patients with mild (6/64, 9%), moderate (22/85, 26%), or severe (1/2, 50%) SLE. Rheumatologists more commonly recommended belimumab for moderate (84/169, 49.7%) and severe (123/169, 72.8%) SLE than for mild SLE (36/169, 21.3%) for patients trying to conceive recently or currently pregnant. Overall, 81.6% (138/169) of the rheumatologists suggested a belimumab washout period before pregnancy of 0-30 days (44/138, 31.9%), 30-60 days (64/138, 46.4%), or >60 days (30/138, 21.7%). Conclusions In this case, crowdsourcing efficiently obtained patient and rheumatologist input, with some patients with SLE continuing to use belimumab during or while planning a pregnancy. There was moderate awareness of the BPR among patients and physicians.

ObjectiveThere 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.MethodsWe 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.ResultsWe 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.ConclusionThere 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.

Understanding a gradable adjective (e.g., big) requires making reference to a comparison class, a set of objects or entities against which the referent is implicitly compared (e.g., big for a Great Dane), but how do listeners decide upon a comparison class? Simple models of semantic composition stipulate that the adjective combines with a noun, which necessarily be- comes the comparison class (e.g., “That Great Dane is big” means big for a Great Dane). We investigate an alternative hypothesis built on the idea that the utility of a noun in an adjectival utterance can be either for reference (getting the listener to attend to the right object) or predication (describing a property of the referent). Therefore, we hypothesize that when the presence of a noun N can be explained away by its utility in reference (e.g., being in the subject position: “That N is big”), it is less likely to set the comparison class. Across three pre-registered experiments, we find evidence that listeners use the noun as a cue to infer comparison classes consistent with a trade-off between reference and predication. This work highlights the complexity of the relation between the form of an utterance and its meaning.

To analyse maternal variables associated with occurrence of small for gestational age (SGA) newborns in pregnancies of women with systemic lupus erythematosus (SLE), considering clinical and laboratory characteristics prior to conception, during gestation and comorbidities.Retrospective cohort study with SLE pregnant patients and singleton deliveries after 22 weeks. SGA newborn was defined as birth weight below 10th percentile and SLE activity at conception and during gestation was measured using the SLE Pregnancy Disease Activity Index (SLEPDAI). Univariate analysis was employed to evaluate individual influence of demographic and clinical variables on the SGA newborn outcome, while variables with p0.20 were included in multivariate regression.Among 151 pregnancies, 28 (18.5%) had SGA newborns. History of proliferative nephritis (RR=3.84, CI 1.63-9.3) and positivity for anti-RNP and anti-Sm antibodies (RR=2.67, CI 1.11-6.43; 2.78, CI 1.44-5.32) were more frequent in the study group. Active proliferative nephritis at conception (RR=3.29, CI 1.75-6.18) and during gestation (RR=3.63, CI 1.97-6.71), as well as complement C3 consumption (RR=2.70, CI 1.09-6.67) and venous pulse therapy with methylprednisolone (RR=20.3, CI 2.18-190), were also associated with SGA newborns, the latter being independently associated in multivariate regression. Adverse perinatal outcomes, such as stillbirths (4.3 times) and neonatal intensive care unit admissions (3.2 times), were more frequent among SGA infants.Active proliferative lupus nephritis during pregnancy was associated with SGA newborns, while its treatment with venous pulse therapy with methylprednisolone may play a significant role in this context. Presence of previous proliferative nephritis, SLEPDAI ≥4, C3 consumption and presence of anti-RNP and anti-Sm antibodies were additional variables associated with SGA newborns in this population.

OBJECTIVE To evaluate mean serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and soluble Flt-1 (sFlt-1) in pregnant patients with systemic lupus erythematosus (SLE) with inactive disease, active lupus nephritis, and preeclampsia for differential diagnosis between these conditions. METHODS Pregnant women with SLE, with singleton pregnancies and no other autoimmune diseases, were classified according to disease activity (inactive SLE and active lupus nephritis) and the presence of preeclampsia. Serum samples were collected within 3 weeks of delivery and frozen for subsequent blinded analysis through the enzyme-linked immunosorbent assay method. RESULTS A total of 71 women were included, with 41 classified as having inactive SLE (group 1; Systemic Lupus Erythematosus Pregnancy Disease Activity Index [SLEPDAI] score

Background Elevated B lymphocyte stimulator (BLyS) levels in patients with systemic lupus erythematosus (SLE) correlate positively with disease activity; BLyS expression is directly linked to interferon (IFN) pathway activation. This post hoc meta-analysis of BLISS-52 and BLISS-76 explored the relationship between baseline BLyS mRNA/protein levels and/or type 1 IFN-inducible gene signature (IFN-1) and responses to the BLyS-targeting monoclonal antibody belimumab in SLE. Methods In BLISS-52 and BLISS-76, patients with autoantibody-positive SLE and a SELENA-SLEDAI score ≥ 6 and receiving stable standard SLE therapy were randomised to intravenous belimumab 10 mg/kg or placebo, plus standard of care (SoC), for 52 or 76 weeks. For this post hoc meta-analysis, patients with an appropriate mRNA sample were stratified by BLyS mRNA expression (tertiles: high/medium/low; revised quantiles: high/low), IFN-1 mRNA expression (high/low) and BLyS protein level (high/low). Co-primary endpoints were correlation between baseline BLyS and IFN-1 mRNA levels and SLE Responder Index (SRI)4 response at week 52 within BLyS/IFN-1 subgroups. Secondary endpoints included time to first severe SELENA-SLEDAI Flare Index (SFI) flare. Results Of 554 patients included in this analysis, 281 had received belimumab and 273 had received placebo. Baseline BLyS and IFN-1 mRNA levels were highly correlated (Spearman’s rank correlation coefficient 0.7799; 95% confidence interval [CI] 0.7451, 0.8106; p p = 0.0153), high BLyS mRNA quantile (OR 1.58; 95% CI 1.02, 2.44; p = 0.0402), high IFN-1 mRNA (OR 1.58; 95% CI: 1.08, 2.31; p = 0.0186) and high BLyS protein (OR 3.57; 95% CI 1.63, 7.83; p = 0.0015) subgroups only. The risk of severe SFI flare was significantly lower with belimumab than placebo in the high BLyS mRNA quantile (hazard ratio [HR] 0.59; 95% CI 0.36, 0.97; p = 0.0371) and high BLyS protein (HR 0.39; 95% CI 0.19, 0.79; p = 0.0090) subgroups. Conclusions This post hoc meta-analysis demonstrated a tendency towards improved response to add-on intravenous belimumab 10 mg/kg versus SoC alone in patients with high baseline BLyS protein and IFN-1 mRNA levels and medium/high BLyS mRNA levels.

Autoimmunity is believed to play an important causative role in the pathogenesis of epilepsy. There are evidences for the presence of autoantibodies in patients with epilepsy. To date, many studies have assessed the presence of antiphospholipid antibodies (aPLs) in epilepsy patients, though the relationship has been inconclusive.The aim of this systematic review and meta-analysis was to evaluate the presence of aPLs in epileptic patients as compared to healthy controls.Five electronic databases (PubMed, Web of Science, Embase, Scopus and Google Scholar) were searched systematically. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). L'Abbé plots were generated to visually inspect heterogeneity while publication bias was evaluated via visualization of contour- enhanced funnel plots, and Begg's and Egger's tests.Based on the inclusion criteria, 14 studies were selected involving 1248 epilepsy patients and 800 healthy controls. The majority of epilepsy was categorised as generalised or partial and none had comorbidity with autoimmune diseases. Significant presence of both anticardiolipin (aCL) antibodies (OR: 5.16, 95% CI: 3.21-8.28, p 0.00001) and anti-β2- glycoprotein I (anti-β2-GPI) antibodies (OR: 2.95, 95% CI: 1.07-8.11, p = 0.04) exhibited comorbid association with epilepsy patients as compared to healthy controls. Subgroup analyses revealed that presence of aCL antibodies was more specifically observed in paediatrics (OR: 4.57, 95% CI: 2.57-8.15, p 0.00001) than adults (OR: 4.24, 95% CI: 1.80-10.01, p = 0.001). The odds of aCL antibody presence was higher in partial epilepsy patients (OR: 7.88, 95% CI: 3.23-19.24, p 0.00001) than that of generalised (OR: 3.76, 95% CI: 2.15-6.59, p 0.00001) and in Asian epileptic patients (OR: 9.56, 95% CI: 2.69-33.95, p = 0.0005) than Europeans (OR: 4.35, 95% CI: 2.74-6.92, p 0.00001). The presence of anti-β2-GPI antibodies was significant in paediatric (OR: 6.44, 95% CI: 1.39-29.89, p = 0.02) and African population with epilepsies (OR: 10.59, 95% CI: 1.22-92.25, p = 0.03). NOS of the majority of the studies (11/14) indicated a high methodological quality. No substantial heterogeneity was observed either from the quantitative analysis or from the L'Abbé plots while no significant publication bias was detected from funnel plots; Begg's and Egger's tests.Since none of the epilepsy subjects exhibited any comorbid autoimmune disorders, significant presence of aCL and anti-β2-GPI antibodies indicate towards their contribution in immune-mediated general pathogenesis of epilepsy.

Summary Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations) add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE) but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy. Resumo A síndrome antifosfolipídide (APS) é uma doença autoimune caracterizada por tromboses e morbidade gestacional associadas à positividade de antiphospholipid antibodies (aPL). A maioria das manifestações da APS está diretamente relacionada aos eventos trombóticos, que podem afetar pequenos, médios ou grandes vasos. Outras manifestações como trombocitopenia, nefropatia, valvulopatia, disfunção cognitiva e úlceras cutâneas (chamadas de manifestações não critérios) agregam significativa morbidade e muitas vezes são refratárias ao tratamento convencional. Embora tenha sido inicialmente descrita em pacientes com lúpus eritematoso sistêmico (LES), a síndrome antifosfolípide também pode ocorrer em pacientes sem outras doenças autoimunes associadas. Apesar do caráter autoimune dessa síndrome, o tratamento da APS ainda é baseado na anticoagulação e na antiagregação plaquetária.

Background: Despite the importance of traditional pulmonary function tests (PFTs) in managing systemic sclerosis (SSc), many patients with pulmonary disease diagnosed by computed tomography (CT) present with normal PFTs. Objective: To evaluate the efficacy of the nitrogen single-breath washout (N2SBW) test in diagnosing SSc and to correlate N2SBW parameters with the PFT indexes used in the follow-up of these patients, clinical data, and CT findings. Methods: Cross-sectional study in which 52 consecutive SSc patients were subjected to spirometry, body plethysmography, analysis of the diffusing capacity for carbon monoxide (DLCO), analysis of respiratory muscle strength, N2SBW testing, and CT analysis. Results: Twenty-eight patients had a forced vital capacity (FVC) that was 120% of the predicted value, while 15 patients had a closing volume/vital capacity (CV/VC) that was >120% of the predicted value. A significant difference in Phase III slopeN2SBW was observed when the patients with predominant traction bronchiectasis and honeycombing were compared to the patients with other CT patterns (pÂ

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.

ObjectivesTreat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.MethodsAn international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%.ResultsThe task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life.ConclusionsThe work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.

Resumo O objetivo destas recomendacoes e orientar o tratamento apropriado de inducao em pacientes com vasculite associada a anticorpos anticitoplasma de neutrofilos (VAA) ativa. As recomendacoes propostas pelo Comite de Vasculopatias da Sociedade Brasileira de Reumatologia para a terapia de inducao para vasculites associadas aos anticorpos anticitoplasma de neutrofilos (VAA), inclusive granulomatose com poliangiite, poliangiite microscopica e vasculite limitada ao rim, foram baseadas em uma revisao sistematica da literatura e na opiniao de especialistas. A revisao da literatura foi feita com as bases de dados Medline (PubMed), Embase e Cochrane para consultar artigos ate outubro de 2016. As diretrizes Prisma ( Preferred Reporting Items for Systematic Reviews and Meta‐Analyses – Principais itens para reportar revisoes sistematicas e metanalises) foram usadas para a revisao sistematica e os artigos foram avaliados de acordo com os niveis de evidencia Oxford. Dezesseis recomendacoes foram feitas em relacao a diferentes aspectos da terapia de inducao para VAA. O objetivo dessas recomendacoes e servir como um guia para decisoes terapeuticas por profissionais da saude no tratamento de pacientes com VAA que apresentem a doenca ativa.

How do children begin to use language to say things they have never heard before? The origins of linguistic productivity have been a subject of heated debate: While generativist accounts posit that children’s early language reflects the presence of syntactic abstractions, constructivist approaches instead emphasize gradual generalization over frequently-heard forms. Here we develop a Bayesian statistical model that measures the degree of abstraction implicit in children’s early use of the determiners “a” and “the.” Our work reveals that many previously-used corpora are too small to adjudicate between these theoretical positions. Several datasets, including the Speechome Corpus—a new ultra-dense dataset for one child—show evidence of low initial levels of productivity and higher levels later in development, however. These findings are consistent with the hypothesis that children lack rich grammatical knowledge at the outset of language learning, but rapidly begin to generalize on the basis of structural regularities in their input.

Background Belimumab (BEL) is approved in adults with active, autoantibody-positive SLE. Phase 2, 3 and long-term extension studies showed a favourable benefit-risk profile. However, numerical differences in the incidence of mortality, infections, hypersensitivity reactions and some psychiatric events warranted a large, focused safety study to assess these events, along with potential for malignancy. Objectives To evaluate all-cause mortality and AESI in patients with SLE receiving intravenous (IV) BEL vs placebo (PBO) over 52 weeks. Methods This study (BASE; BEL115467; NCT01705977) randomised adults with SLE (1:1) to monthly BEL 10 mg/kg IV or PBO, plus standard of care, for 48 weeks. No minimum SELENA-SLEDAI disease activity was required and no exclusions for previous psychiatric conditions were made. Differences in rates (95% CI) of mortality and other pre-specified AESI (malignancies, serious infections, opportunistic infections and other infections of interest, serious depression, suicidality [C-SSRS], and serious infusion/hypersensitivity reactions) on-treatment (first to last dose +28 days) were assessed. For on-treatment serious suicidal ideation/behaviour and self-injury events (per sponsor adjudication), and on-study (first dose to end of Week 52 study follow-up) suicidal ideation/behaviour (C-SSRS), differences (95% CI) vs PBO were calculated post hoc. Results 4003 patients received ≤1 dose. Baseline demographics and disease characteristics were similar between groups. On-treatment mortality and pre-specified AESI rates are shown in the Table 1 below. Overall rates of on-treatment AESIs were similar between groups, except for serious depression and serious infusion/hypersensitivity reactions. On-treatment deaths were most frequently caused by infection (3 [0.15%] PBO vs 9 [0.45%] BEL); on-study deaths occurred in 22 (1.10%) PBO and 13 (0.65%) BEL patients (difference [95% CI]: -0.45 [-1.03, 0.13]). On-treatment serious suicidal ideation/behaviour and self-injury events were reported for 5 (0.25%) PBO and 15 (0.75%) BEL patients (difference [95% CI]: 0.50 [0.06, 0.94]); on-study suicidal ideation/behaviour (C-SSRS) occurred in 39 (1.96%) PBO and 48 (2.43%) BEL patients (difference [95% CI]: 0.47 [-0.44, 1.38]). No suicide-related deaths were reported. Conclusion In this double-blind, placebo-controlled (1:1) safety study, which is the largest SLE clinical study to date with 4003 patients, on-treatment all-cause mortality, infection and malignancy AESI rates were similar between BEL and PBO, with imbalances observed in serious depression, serious suicidal ideation/behaviour and self-injury events, and serious infusion/hypersensitivity reactions. Acknowledgement We acknowledge the BASE Study Group. Study funding: GSK. Disclosure of Interests Saira Sheikh Consultant for: GSK, Morton Scheinberg: None declared, James Cheng-Chung Wei Grant/research support from: TSH Biopharm, Abbvie, BMS, Celgene, Janssen, Novartis, Pfizer and UCB, Consultant for: TSH biopharm, Abbvie, BMS, Celgene, Chugai, Eisai, Janssen, Novartis, Pfizer, Sanofi-Aventis and UCB pharma, Dana Tegzova: None declared, William Stohl Grant/research support from: GSK, Consultant for: Janssen R&D, Tamara Mucenic Grant/research support from: GSK, Janssen, Roche, Eli Lilly, Pfizer, Amgen, Consultant for: Janssen, Roche, UCB, Novartis, Speakers bureau: Janssen, Roche, UCB, Novartis, Abbvie, Pfizer, Roger Levy Shareholder of: GSK, Employee of: GSK, Damon Bass Shareholder of: GSK, Employee of: GSK, Jorge Ross Terres Shareholder of: GSK, Employee of: GSK at the time of study, Rajesh Punwaney Shareholder of: GSK, Employee of: GSK, Julia Harris Shareholder of: GSK, Employee of: GSK, Kevin Thorneloe Shareholder of: GSK, Employee of: GSK, Beulah Ji Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK

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 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 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.

Background The APS ACTION International Clinical Database and Repository includes a secure web-based data capture system storing patient information including demographics, antiphospholipid antibodies (aPL)-related medical history, and aPL tests. Despite efforts at harmonization, inter-assay variability remains a problem in aPL testing. As a clinical repository open to researchers, ensuring comparability between assays and consistency in results between APS ACTION laboratories is essential to the validity of studies emerging from this network. Objective To assess the level of agreement between an aPL-registry inclusion and core laboratory (core lab) anticardiolipin antibody (aCL) and anti-β2-glycoprotein-I antibody (aβ2GPI) ELISA testing results. Methods Patients are recruited from 25 international centers based on positive aPL tests at inclusion. All samples are retested at the corresponding national APS ACTION core lab to confirm aPL positivity based on standard validated protocols. We analysed the categorical agreement, degree of linear association, and correlation between inclusion (local laboratory) and core lab aPL tests. Samples were included in this study only if results of aPL testing with ELISA at baseline were available. Results 497 registry samples underwent confirmatory aPL tests. Categorical agreement between the inclusion and core lab values, as expressed by Cohen's kappa coefficients, ranged between 0.61 and 0.80 (as substantial agreement). The correlation between quantitative results in the aCL and aβ2GPI was better for IgM and IgA compared to IgG (Spearman rho 0.789 and 0.666 vs. 0.600 for aCL and rho 0.892 and 0.744 vs. 0.432 for aβ2GPI). Conclusions The results of inclusion for aCL and aβ2GPI tests used for recruitment into the registry were in agreement to the results obtained by the APS ACTION core laboratories; aCL and aβ2GPI results showed very good categorical agreement. This agreement increased when considering high titer (>40 units) samples. APS ACTION is a reliable and useful research resource for APS.

Objective To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. Design Retrospective study. Setting The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. Population Women with Ob-APS. Methods Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). Main outcome measures Risk factors for thrombosis and aGAPSS. Results Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. Conclusion Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. Tweetable abstract More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.

Background:Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease resulting in increased morbidity and mortality and reduced health-related quality of life (HRQoL). Patients with SLE are at risk of developing irreversible long-term organ damage (LTOD) caused by both disease activity and cumulative medication toxicities. Data regarding the overall disease burden and impact of LTOD in patients with SLE are limited.Objectives:The primary objective of this qualitative study was to develop a conceptual model to describe the burden experienced by patients with SLE and LTOD.Methods:This study (GSK Study 209754) was conducted in three phases. First, a targeted literature review was performed to aid the development of an initial draft conceptual model. Key opinion leaders (KOLs) with experience in SLE and LTOD were then interviewed to assess the clarity, language, comprehensibility, and potential use of the conceptual model, and to help shape the patient interview materials. Finally, one-on-one interviews were performed with patients with SLE and LTOD in any of the 12 organ areas (defined by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), to gather patient perspectives on the common symptoms, functional impacts, treatment experiences, and HRQoL factors associated with LTOD. Data from the interviews were coded and analysed using NVivo software to identify patterns in responses concerning the key concepts of the overall patient burden of LTOD, and used to identify concepts to include in the model.Results:The literature review produced the preliminary conceptual model of LTOD. Results of the KOL interviews (n=5 clinicians and n=1 patient advocate) indicated that the preliminary conceptual model broadly captured the patient experience of LTOD. KOLs emphasised the difference between SLE activity (flares) and LTOD; the conceptual model was subsequently updated in accordance with these recommendations. Interviews conducted with patients with confirmed single (n=9) and multiple LTOD (n=31) indicated that the burden of LTOD associated with SLE was more severe, debilitating, and life threatening than that caused by SLE flares. Almost all patients (39/40) reported aspects of their lives that were more severely affected since their LTOD diagnosis. All 40 patients reported LTOD-related physical impacts, which often affected patients’ ability to perform everyday tasks. The most frequent physical impacts reported were a loss of vitality (39/40), long-term complications (e.g. unstable blood pressure, extreme pain, poor mobility, inflammation, dialysis, infection; 36/40), and severe fatigue (29/40). Cognitive impairments that became more pronounced after their LTOD diagnosis were reported by 27/40 of patients. Typically characterised as “brain fog”, these impairments were described as slower cognitive processing, forgetfulness, confusion, and aphasia. Economic impacts associated with LTOD included patients’ inability to work (31/40), costs of care (33/40), and non-medical-related costs (17/30). Psychosocial impacts reported by patients with LTOD affected their emotional state (39/40), ability to socialise (40/40) and relationships (30/40). Additionally, 30/40 patients reported symptoms as more severe since their LTOD diagnosis, including pain (14/40), fatigue (9/40), and oedema (8/40). Patients’ treatment goals were largely aligned with their experienced impacts of LTOD, including managing the disease and symptoms (25/40), limiting further organ damage (15/40), and improving HRQoL (11/40).Conclusion:The findings from this research clearly indicate that the patient burden of LTOD far surpasses that of SLE without LTOD. These data were incorporated and refined into a conceptual model that fully represents the patient experience of LTOD. The model will help researchers, clinicians, and patients to better understand the impact of SLE-related LTOD progression.Funding:GSKAcknowledgements:Medical writing assistance was provided by Casmira Brazaitis, PhD, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.Disclosure of Interests:Lynne Broderick Consultant of: GSK, Wen-Hung Chen Shareholder of: GSK, Employee of: GSK, Roger Levy Shareholder of: GSK, Employee of: GSK, April Foster Consultant of: GSK, Cindy Umanzor Consultant of: GSK, Deven Chauhan Shareholder of: GSK, Employee of: GSK

The crucial issue for a better pregnancy outcome in women with autoimmune rheumatic diseases is appropriate planning, with counseling of the ideal timing and treatment adaptation. Drugs used to treat rheumatic diseases may interfere with fertility or increase the risk of miscarriages and congenital abnormalities. MTX use post-conception is clearly linked to abortions as well as major birth defects, so it should be stopped 3months before conception. Leflunomide causes abnormalities in animals even in low doses. Although in humans, it does not seem to be as harmful as MTX, when pregnancy is detected in a patient on leflunomide, cholestyramine is given for washout. Sulfasalazine can be used safely and is an option for those patients who were on MTX or leflunomide. Azathioprine is generally the immunosuppressive of choice in many high-risk pregnancy centers because of the safety profile and its steroid-sparing property. Cyclosporine and tacrolimus can also be used as steroid-sparing agents, but experience is smaller. Although prednisone and prednisolone are inactivated in the placenta, we try to limit the dose to the minimal effective one, to prevent side effects. Antimalarials have been broadly studied and are safe during pregnancy and breastfeeding. Among biologic disease modifying anti-rheumatic agents (bDMARD), the anti-TNFs that have been used for longer are the ones with greater experience. The large monoclonal antibodies do not cross the placenta in the first trimester, and after conception, the decision to continue medication should be taken individually. The experience is larger in women with inflammatory bowel diseases, where anti-TNF is generally maintained at least until 30weeks to reduce fetal exposure. Live vaccines should not be administrated to the infant in the first 6months of life. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab, ustekinumab, belimumab, and tofacitinib are limited and their use in pregnancy cannot currently be recommended.

ResumoA esclerose sistêmica (ES) é uma doença autoimune crônica de alta morbimortalidade. Ainda que a ciclofosfamida seja eficaz, para casos graves e refratários há demanda para novos tratamentos. A terapia biológica com depleção de células B com rituximabe (RTX) demonstrou eficácia para tal demanda em estudos abertos.ObjetivoAvaliar retrospectivamente todos os pacientes que fizeram uso do RTX para tratamento de ES em nosso centro.Pacientes e métodosForam avaliados retrospectivamente todos os prontuários de pacientes com ES que fizeram uso de RTX para tratamento da ES de janeiro de 2009 a janeiro de 2015. Dados de acometimento sistêmico, cutâneo, pulmonar e laboratoriais antes e seis meses após a primeira infusão de RTX foram coletados.ResultadosDez pacientes receberam o tratamento no período de estudo e foram incluídos na presente série de casos. Todos os pacientes tinham a forma difusa da doença. Cinco pacientes tinham formas iniciais (tempo de doença menor ou igual a quatro anos) e rapidamente progressiva da doença e cinco receberam o RTX em fases tardias da doença. Houve estabilização do quadro pulmonar em ambos os grupos de pacientes e redução no escore cutâneo nos pacientes com formas iniciais da doença.DiscussãoSimilar ao encontrado em estudos prévios, o RTX foi eficaz no tratamento de formas iniciais e rapidamente progressivas da ES. Verificamos também benefício em pacientes com longa duração da doença.AbstractSystemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Although cyclophosphamide is effective for severe and refractory cases, there is demand for new treatments. The biological treatment with B‐cell depletion with rituximab (RTX) has demonstrated efficacy for this demand in open‐label studies.ObjectiveThis study was conducted with the aim to retrospectively evaluate all patients who used RTX for the treatment of SSc in our center.Patients and methodsWe retrospectively evaluated medical records of all patients with SSc who used RTX to treat this disease from January 2009 to January 2015. Systemic, cutaneous, and pulmonary involvement data and laboratory results before and six months after the first infusion of RTX were collected.ResultsTen patients received treatment during the study period and were included in this series. All patients had a diffuse form of the disease. Five patients suffered from an early (duration of disease shorter or equal to four years), rapidly progressive disease, and another five received RTX at late stages of the disease. In both groups of patients, stabilization of the pulmonary picture was observed, with a fall in the skin score in those patients with early forms of the disease.DiscussionSimilar to findings in previous studies, RTX was effective in treating early and rapidly progressive forms of SSc. We also found that patients with long‐term illness may benefit from the treatment.

The term autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) or Shoenfeld's syndrome refers to a wide group of immune-mediated diseases triggered by external agents. Several substances, such as vaccine adjuvants, squalene and silicone implants, are implied in the pathogenesis of ASIA syndrome. Treatment and prognosis of this complex condition are not completely known due to lack of good quality evidence. After a brief introductory literature review on ASIA, we report here two cases of patients that developed rapidly progressive systemic sclerosis clinical features after multiple intramuscular local injections of a substance recommended by a non-medical professional called ADE. ADE is an oily vitamin complex for veterinary use, and it was used in these cases for cosmetic muscular definition and enhancement purpose. To our knowledge, this is the first paper to describe the relation between injections of ADE and the development of ASIA with severe systemic sclerosis phenotype. Further investigation is needed to better understand the pathophysiology and to provide the basis for the treatment of this condition.

The eye is divided anatomically in three layers: an outer or fibrous layer (cornea/sclera), middle or vascular layer (uvea — iris, ciliary body, and choroid) and an inner or sensorineural layer (retina). They compose the several anatomic and functional layers that enable the immune protection of the eye. The first layer involves an intact anatomic border with the blood–ocular barrier and immunosuppressive neuropeptides in the native aqueous humor. The second layer trusts on the capability of the eye to reestablish an immunosuppressive micro-environment by activating latent TGF-β and reestablishing the anterior chamber-associated immune deviation. The third layer involves a mechanism that is not yet completely recognized, but that has the ability to overcome a predominantly Th1 intraocular immune response and to reestablish anterior chamber-associated immune deviation. Understanding the comprehensive mechanisms of these pathways, will lead to the development of new treatments strategies in order to prevent damage to the eye from persistent or exacerbated inflammation, directed at first to pathogens, but that may develop an autoimmune reaction.

Objective To investigate the effect of rituximab on microcirculation in long-term SSc. Results Four patients with diffuse SSc over 3 years of disease received rituximab cycles of two 1-g infusions every 6 months for 2 years. Videocapillaroscopy was performed at baseline, 12 months, and 24 months and semi-quantitative scoring of videocapillaroscopy abnormalities was performed and the microangiopathy evolution score (MES: range 0–9) was calculated. The mean disease duration was 5 years (range 3–15). On videocapillaroscopy, giant capillaries and hemorrhages remained stable from baseline to 24 months. Capillary loss, abnormally-shaped capillaries, and MES stabilized at 12 months and increased by 24.5% and 28% at 24 months. Rituximab improves microcirculation in long-term SSc. Stabilization and reduced progression of microcirculation abnormalities were achieved at 12 and 24 months, respectively. Electronic supplementary material The online version of this article (10.1186/s13104-018-3994-1) contains supplementary material, which is available to authorized users.

This article describes three complicated cases in rheumatology and pregnancy. The first case elucidates the challenges in treating SLE in conjunction with pulmonary arterial hypertension, while the second case features an SLE-affected pregnancy with development of portal hypertension secondary to portal vein thrombosis related to APS. The third case is a pregnant woman with stable SLE who developed thrombotic microangiopathy caused by atypical haemolytic uraemic syndrome, and failed to improve despite multiple measures including biopsy and elective preterm delivery. There are grave and unique challenges for women with autoimmune disease, but adverse outcomes can sometimes be avoided with careful and multidisciplinary medical management. Pre-conception counselling with regard to medications and disease treatment should also include discussion of the advisability of pregnancy, which may be difficult for a patient, but present the best course for optimizing health outcomes.

Background Non-United States completers of the Phase 3 BLISS-52 (BEL110752) and BLISS-76 (BEL110751) studies could continue treatment with BEL. Objectives To evaluate long-term safety, tolerability and organ damage progression in patients with SLE treated with BEL. Methods In this multicentre, open-label long-term study (BEL112234/NCT00712933), patients received intravenous BEL every 4 weeks, plus standard SLE therapy. Safety was assessed at each visit. Organ damage (Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index [SDI]) was assessed as a safety endpoint every 48 weeks. The study continued until BEL was commercially available in each patient’s country and included an 8 week follow–up period. Results In total, 738 patients entered the long-term study and were treated for up to 9 years (3352 patient-years). Of these, 735 (99.6%) received ≥1 dose of BEL; the mean (SD) number of infusions was 56.4 (27.02). The incidence of adverse events (AEs) remained stable or declined over time (table 1). The most common AEs were headache (n=205, 27.9%), nasopharyngitis (n=155, 21.1%), diarrhoea (n=143, 19.5%), arthralgia (n=136, 18.5%) and influenza (n=134, 18.2%). Sixty-nine patients (9.4%) experienced an AE resulting in discontinuation of BEL or study withdrawal. Eleven deaths occurred, one of which (cardiogenic shock) was possibly related to BEL. Three serious AEs of suicide attempt/ideation (0.4%) occurred. The mean (SD) SDI score was 0.6 (1.02) at baseline (prior to the first dose of BEL). At Year 8 87.7% of patients had no change in SDI score from baseline, indicating low organ damage accrual (figure 1). aNumber of patients; bincluded opportunistic infections, tuberculosis, herpes zoster (recurrent and disseminated) and sepsis; ctwo deaths during post-treatment follow-up. Conclusions BEL displayed a stable safety profile with no new safety signals. There was minimal organ damage progression. Acknowledgements Study funded by GSK. Emma Hargreaves, MA, Fishawack Indicia Ltd, UK, provided editorial assistance funded by GSK. Disclosure of Interest R. Van Vollenhoven Grant/research support from: GSK, Consultant for: GSK, S. Navarra Speakers bureau: GSK, R. Levy Employee of: BLISS-52 investigator and GSK employee since ,Jan 2018 M. Thomas Grant/research support from: GSK, Consultant for: GSK, A. Heath Shareholder of: GSK, Employee of: GSK, T. Lustine Shareholder of: GSK, Employee of: GSK, A. Adamkovic Shareholder of: GSK, Employee of: GSK, J. Fettiplace Shareholder of: GSK, Employee of: GSK (at the time of study), M. L. Wang Shareholder of: GSK, Employee of: GSK, B. Ji Shareholder of: GSK, Employee of: GSK, D. Roth Shareholder of: GSK, Employee of: GSK

Tuberculosis (TB) is a millenarian chronic infection and, yet, remains a major global health problem. The interaction between systemic lupus erythematosus (SLE) and TB is complex, as one seems to be a risk factor for the development of the other. SLE patients are more likely to develop TB, that is more frequently extrapulmonary, with more extensive pulmonary involvement, and with a higher relapse rate.Different studies suggest that TB is more prevalent in SLE patients and that TB may actually be a risk factor for the development of the disease. Molecular and epidemiological data suggest that TB may be involved in the pathogenesis of SLE.We reviewed the most relevant aspects of TB infection in SLE patients, including the burden of TB, its role in inducing flare and its perpetuation, risk evaluation and prevention, and pearls and pitfalls when assessing extrapulmonary TB in SLE patients. We conclude that a high suspicion of TB in SLE patients from endemic countries should be kept in mind, especially in those with nephritis and high cumulative doses of corticosteroids.

Modern medicine is in a continuous state of flux given the relentless development of new evidence; thus, it is quite difficult for clinicians to remain abreast of all advances as they happen. Trustworthy clinical practica guidelines (CPGs) rigorously developed following a transparent methodology (http://www.gradeworkinggroup.org/) and including the best available evidence represent one of the best solutions to overcome these problems...

Background In scleroderma, excessive collagen production can alter tracheal geometry, and computed tomography (CT) volumetry of this structure may aid in detecting possible abnormalities. The objectives of this study were to quantify the morphological abnormalities in the tracheas of ​​patients with scleroderma and to correlate these findings with data on clinical and pulmonary function. Methods This was a cross-sectional study in which 28 adults with scleroderma and 27 controls matched by age, gender and body mass index underwent chest CT with posterior segmentation and skeletonization of the images. In addition, all participants underwent pulmonary function tests and clinical evaluation, including the modified Rodnan skin score (mRSS). Results Most patients (71.4%) had interstitial lung disease on CT. Compared to controls, patients with scleroderma showed higher values ​​in the parameters measured by CT trachea volumetry, including area, eccentricity, major diameter, minor diameter, and tortuosity. The tracheal area and equivalent diameter were negatively correlated with the ratio between forced expiratory flow and forced inspiratory flow at 50% of forced vital capacity (FEF50%/FIF50%) (r = -0.44, p = 0.03 and r = -0.46, p = 0.02, respectively). The tracheal tortuosity was negatively correlated with peak expiratory flow (r = -0.51, p = 0.008). The mRSS showed a positive correlation with eccentricity (r = 0.62, p < 0.001) and tracheal tortuosity (r = 0.51, p = 0.007), while the presence of anti-topoisomerase I antibody (ATA) showed a positive correlation with tracheal tortuosity (r = 0.45, p = 0.03). Conclusions In a sample composed predominantly of scleroderma patients with associated interstitial lung disease, there were abnormalities in tracheal geometry, including greater eccentricity, diameter and tortuosity. In these patients, abnormalities in the geometry of the trachea were associated with functional markers of obstruction. In addition, tracheal tortuosity was correlated with cutaneous involvement and the presence of ATA.

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings. Fil: Pons Estel, Bernardo A.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina Fil: Bonfa, Eloisa. Universidade de Sao Paulo; Brasil Fil: Soriano, Enrique R.. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; Argentina Fil: Cardiel, Mario H.. Centro de Investigación Clínica de Morelia; México Fil: Izcovich, Ariel. Hospital Alemán; Argentina Fil: Popoff, Federico. Hospital Aleman; Argentina Fil: Criniti, Juan M.. Hospital Alemán; Argentina Fil: Vásquez, Gloria. Universidad de Antioquia; Colombia Fil: Massardo, Loreto. Universidad San Sebastián; Chile Fil: Duarte, Margarita. Hospital de Clínicas; Paraguay Fil: Barile Fabris, Leonor A.. Hospital Angeles del Pedregal; México Fil: García, Mercedes A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Amigo, Mary Carmen. Centro Médico Abc; México Fil: Espada, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Catoggio, Luis J.. Hospital Italiano. Instituto Universitario. Escuela de Medicina; Argentina Fil: Sato, Emilia Inoue. Universidade Federal de Sao Paulo; Brasil Fil: Levy, Roger A.. Universidade do Estado de Rio do Janeiro; Brasil Fil: Acevedo Vásquez, Eduardo M.. Universidad Nacional Mayor de San Marcos; Perú Fil: Chacón Díaz, Rosa. Policlínica Méndez Gimón; Venezuela Fil: Galarza Maldonado, Claudio M.. Corporación Médica Monte Sinaí; Ecuador Fil: Iglesias Gamarra, Antonio J.. Universidad Nacional de Colombia; Colombia Fil: Molina, José Fernando. Centro Integral de Reumatología; Colombia Fil: Neira, Oscar. Universidad de Chile; Chile Fil: Silva, Clóvis A.. Universidade de Sao Paulo; Brasil Fil: Vargas Peña, Andrea. Hospital Pasteur Montevideo; Uruguay Fil: Gómez Puerta, José A.. Hospital Clinic Barcelona; España Fil: Scolnik, Marina. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; Argentina Fil: Pons Estel, Guillermo J.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina. Hospital Provincial de Rosario; Argentina Fil: Ugolini Lopes, Michelle R.. Universidade de Sao Paulo; Brasil Fil: Savio, Verónica. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; Argentina Fil: Drenkard, Cristina. University of Emory; Estados Unidos Fil: Alvarellos, Alejandro J.. Hospital Privado Universitario de Córdoba; Argentina Fil: Ugarte Gil, Manuel F.. Universidad Cientifica del Sur; Perú. Hospital Nacional Guillermo Almenara Irigoyen; Perú Fil: Babini, Alejandra. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; Argentina Fil: Cavalcanti, André. Universidade Federal de Pernambuco; Brasil Fil: Cardoso Linhares, Fernanda Athayde. Hospital Pasteur Montevideo; Uruguay Fil: Haye Salinas, Maria Jezabel. Hospital Privado Universitario de Córdoba; Argentina Fil: Fuentes Silva, Yurilis J.. Universidad de Oriente - Núcleo Bolívar; Venezuela Fil: Montandon De Oliveira E Silva, Ana Carolina. Universidade Federal de Goiás; Brasil Fil: Eraso Garnica, Ruth M.. Universidad de Antioquia; Colombia Fil: Herrera Uribe, Sebastián. Hospital General de Medellin Luz Castro de Gutiérrez; Colombia Fil: Gómez Martín, DIana. Instituto Nacional de la Nutrición Salvador Zubiran; México Fil: Robaina Sevrini, Ricardo. Universidad de la República; Uruguay Fil: Quintana, Rosana M.. Hospital Provincial de Rosario; Argentina. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina Fil: Gordon, Sergio. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; Argentina Fil: Fragoso Loyo, Hilda. Instituto Nacional de la Nutrición Salvador Zubiran; México Fil: Rosario, Violeta. Hospital Docente Padre Billini; República Dominicana Fil: Saurit, Verónica. Hospital Privado Universitario de Córdoba; Argentina Fil: Appenzeller, Simone. Universidade Estadual de Campinas; Brasil Fil: Dos Reis Neto, Edgard Torres. Universidade Federal de Sao Paulo; Brasil Fil: Cieza, Jorge. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: González Naranjo, Luis A.. Universidad de Antioquia; Colombia Fil: González Bello, Yelitza C.. Ceibac; México Fil: Collado, María Victoria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Sarano, Judith. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Sattler, María E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina Fil: Gamboa Cárdenas, Rocio V.. Hospital Nacional Guillermo Almenara Irigoyen; Perú Fil: Cairoli, Ernesto. Universidad de la República; Uruguay Fil: Conti, Silvana M.. Hospital Provincial de Rosario; Argentina Fil: Amezcua Guerra, Luis M.. Instituto Nacional de Cardiologia Ignacio Chavez; México Fil: Silveira, Luis H.. Instituto Nacional de Cardiologia Ignacio Chavez; México Fil: Borba, Eduardo F.. Universidade de Sao Paulo; Brasil Fil: Pera, Mariana A.. Hospital Interzonal General de Agudos General San Martín; Argentina Fil: Alba Moreyra, Paula B.. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina Fil: Arturi, Valeria. Hospital Interzonal General de Agudos General San Martín; Argentina Fil: Berbotto, Guillermo A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina Fil: Gerling, Cristian. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; Argentina Fil: Gobbi, Carla Andrea. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gervasoni, Viviana L.. Hospital Provincial de Rosario; Argentina Fil: Scherbarth, Hugo R.. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; Argentina Fil: Brenol, João C. Tavares. Hospital de Clinicas de Porto Alegre; Brasil Fil: Cavalcanti, Fernando. Universidade Federal de Pernambuco; Brasil Fil: Costallat, Lilian T. Lavras. Universidade Estadual de Campinas; Brasil Fil: Da Silva, Nilzio A.. Universidade Federal de Goiás; Brasil Fil: Monticielo, Odirlei A.. Hospital de Clinicas de Porto Alegre; Brasil Fil: Seguro, Luciana Parente Costa. Universidade de Sao Paulo; Brasil Fil: Xavier, Ricardo M.. Hospital de Clinicas de Porto Alegre; Brasil Fil: Llanos, Carolina. Universidad Católica de Chile; Chile Fil: Montúfar Guardado, Rubén A.. Instituto Salvadoreño de la Seguridad Social; El Salvador Fil: Garcia De La Torre, Ignacio. Hospital General de Occidente; México Fil: Pineda, Carlos. Instituto Nacional de Rehabilitación; México Fil: Portela Hernández, Margarita. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; México Fil: Danza, Alvaro. Hospital Pasteur Montevideo; Uruguay Fil: Guibert Toledano, Marlene. Medical-surgical Research Center; Cuba Fil: Reyes, Gil Llerena. Medical-surgical Research Center; Cuba Fil: Acosta Colman, Maria Isabel. Hospital de Clínicas; Paraguay Fil: Aquino, Alicia M.. Hospital de Clínicas; Paraguay Fil: Mora Trujillo, Claudia S.. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Muñoz Louis, Roberto. Hospital Docente Padre Billini; República Dominicana Fil: García Valladares, Ignacio. Centro de Estudios de Investigación Básica y Clínica; México Fil: Orozco, María Celeste. Instituto de Rehabilitación Psicofísica; Argentina Fil: Burgos, Paula I.. Pontificia Universidad Católica de Chile; Chile Fil: Betancur, Graciela V.. Instituto de Rehabilitación Psicofísica; Argentina Fil: Alarcón, Graciela S.. Universidad Peruana Cayetano Heredia; Perú. University of Alabama at Birmingahm; Estados Unidos

The First PANLAR Rheumatology Review Course was held in Barranquilla, Colombia, in April 2015. Researchers, rheumatologists, epidemiologists, and a variety of allied professionals and patients attended the meeting. The scientific program included plenary sessions and symposia delivered by renowned experts in the field, followed by an interactive forum of discussion during 2 days.A broad spectrum of topics was discussed, reflecting the current challenges and opportunities for diagnosis and treatment of rheumatoid arthritis (RA) in Latin America. The scientific program included not only traditional disease aspects, but also social implications, research projects, and educational characteristics, patient perspectives, and novel care models, emphasizing the need for training human resources and proposing unique approaches to RA health care in Latin America, therefore helping us to increase and improve the knowledge and understanding of the characteristics of this health condition in the region, thus promoting and encouraging equity, quality, and efficiency of RA health care.