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Aims: To validate an SPE-ultra-HPLC-MS/MS method for thalidomide (THD) measurement in dried plasma spot (DPS). Methods: Extraction included acetonitrile/water clean-up and online SPE. The LOD, LLOQ, linearity, precision, accuracy, recovery, matrix effect, process efficiency, carryover, stability, drug interference and dilution integrity were assessed. Results: The method was linear from 50 to 2000 ng/ml with a LOD of 20 ng/ml and LLOQ of 50 ng/ml. The coefficient of variation for precision was 0.4–7.9% for intra-assay and 1.3–8.9% for interassay, and accuracy was 81.4–97.1%. Adequate matrix effect (100.6–107.0%), recovery (88.7–105.0%) and process efficiency (91.3–109.3%) were registered. DPS was stable for 14 days at room temperature and 45°C ,and for 4 months at -80°C. The method was applied to quantify THD in both wet plasma and DPS from patients with cutaneous lupus receiving THD treatment. The difference between THD wet plasma and DPS concentration was

ObjectiveTo determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response.MethodsAdult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination.ResultsARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (pConclusionsWe provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX.Trial registration numberNCT04754698.

To date, the only study that has assessed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 mRNA) vaccine in systemic lupus erythematosus (SLE) observed a moderate response, but the sample size precluded an accurate analysis of the effect of individual drugs. Therefore, we evaluated the immunogenicity of an inactivated SARS-CoV-2 vaccine (Sinovac-CoronaVac) and the influence of different medications in SLE. Safety was also assessed.We conducted a prospective controlled study of 232 SARS-CoV-2-naive SLE patients and 58 SARS-CoV-2-naive controls who were vaccinated with 2 doses of Sinovac-CoronaVac with a 28-day interval (day 0/day 28 [D0/D28]). Immunogenicity analysis at D0/D28 and D69 included anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralizing antibodies (NAb) positivity. The influence of individual drugs on immune response and safety was assessed.Patients and controls were well balanced for age (P = 0.771). At D69, SLE patients showed a moderate SC (70.2% versus 98.1%; P 0.001) and moderate frequency of NAb positivity (61.5% versus 84.6%; P = 0.002), although both frequencies were lower than in controls. Factors associated with lower SC in univariate analysis at D69 were prednisone use (odds ratio [OR] 0.215 [95% confidence interval (95% CI) 0.108-0.427], P 0.001) and mycophenolate mofetil (MMF) use (OR 0.201 [95% CI 0.107-0.378], P 0.001), whereas hydroxychloroquine (HCQ) use led to a 2.5 increase in SC (P = 0.011). SLE patients who were receiving HCQ monotherapy had similar SC to controls at D69 (100% versus 98.1%; P = 1.000). In multivariate analysis, prednisone and MMF use were independently associated with lower SC (P 0.001) and NAb positivity (P 0.001). Safety analysis revealed no moderate/severe adverse events.Sinovac-CoronaVac has a moderate immunogenicity in SARS-CoV-2-naive SLE patients with an excellent safety profile. We further demonstrate that HCQ may improve SC, whereas prednisone and MMF had a major deleterious effect in vaccine response, reinforcing the need to investigate the role of temporary MMF withdrawal or a vaccine-booster dose (ClinicalTrials.gov identifier: NCT04754698).

Background The VI Brazilian Consensus on Autoantibodies against HEp-2 cells for determination of autoantibodies against cellular constituents on HEp-2 cells was held on September, 2019, in Fortaleza (CE, Brazil). The guidelines in this edition were formulated by the group of Brazilian experts discussing the classification of complex patterns, the classification of the nuclear discrete dots (few and multiple), the identification of the discrete fine speckled pattern (AC-4a) and improvements on the ANA report. Mainbody Sixteen Brazilian researchers and experts from universities and clinical laboratories representing the various geographical regions of Brazil participated in the meeting. Four main topics were discussed: (1) How to classify patterns with fluorescence in more than one cell compartment considering three relevant categoris: composite patterns, mixed patterns and multiple patterns; (2) The splitting of the discrete nuclear dots pattern into the multiple discrete nuclear dots (AC-6) and few discrete nuclear dots (AC-7) patterns, respectively; (3) Inclusion of a novel nuclear pattern characterized by discrete fine speckled pattern highly associated with antibodies to SS-A/Ro60, classified as AC-4a. In addition, adjustments on the Brazilian Consensus nomenclature were implemented aiming to harmonize the designation of some patterns with the International Consensus on ANA Patterns (ICAP). Furthermore, the designations of the PCNA-like pattern (AC-13), CENP-F-like pattern (AC-14) and Topo I-like pattern (AC-29) were adjusted in accordance to ICAP. Finally, there was a recommendation for adjustment in the test report in order to address the status of nuclear envelope staining. For all topics, the aim was to establish specific guidelines for laboratories and clinicians. All recommendations were based on consensus among participants. All recommendations from the V Consensus were maintained and there was relevant progress in the BCA/HEp-2 guidelines and further harmonization with ICAP. Conclusion The VI BCA/HEp-2 edition was successful in establishing important recommendations regarding the classification of complex patterns, in supporting the identification of a novel pattern within the AC-4 group and in the harmonization process with the ICAP terminology.

Background Few prospective studies in cutaneous and systemic lupus erythematosus (CLE/SLE) assessed thalidomide-induced peripheral neuropathy (TiPN) incidence/reversibility, and most have not excluded confounding causes neither monitored thalidomide plasma levels. Objectives To evaluate TiPN incidence/reversibility, coasting effect and its association with thalidomide plasma levels in CLE/SLE. Methods One-year prospective study of thalidomide in 20 CLE/SLE patients without pregnancy potential, with normal nerve conduction study (NCS), and excluded other PN causes. Thalidomide levels were determined by high-performance liquid chromatography/tandem mass spectrometry. Results Twelve patients (60%) developed TiPN: 33.3% were symptomatic and 66.6% asymptomatic. Half of this latter group developed coasting effect (TiPN symptoms 1-3 months after drug withdrawal). The main predictive factors for TiPN were treatment duration ≥6 months (p = 0.025) and cumulative dose (p = 0.023). No difference in plasma thalidomide levels between patients with/without TiPN was observed (p = 0.464). After drug withdrawal, 75% symptomatic TiPN patients improved their symptoms. Seven TiPN patients underwent an additional NCS after drug withdrawal: 42.8% worsened NCS, 14.2% was stable, and 42.8% had improved NCS. Conclusion Our data provides novel evidence of coasting effect in half of asymptomatic patients with TiPN. The irreversible nature of this lesion in 25% of TiPN patients reinforces the relevance of early NCS monitoring, and suggests thalidomide use solely as a bridge for other effective therapy for refractory cutaneous lupus patients.

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.

Sjogren's Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients.

Objective To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P 65 years, P Conclusion The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Objectives It is unknown if hydroxychloroquine blood level dynamics impact flare rates in lupus nephritis patients. We prospectively evaluated hydroxychloroquine levels to determine which blood-based patterns are more associated with disease activity. Methods In total, 82 lupus nephritis patients under a prescribed hydroxychloroquine dose of 4–5.5 mg/kg actual body weight (maximum 400 mg/day) for ≥3 months were evaluated at baseline and 7 months. Hydroxychloroquine blood levels were determined by liquid chromatography-tandem mass spectrometry. Flare was defined as increase ≥3 in the Systemic Lupus Erythematosus Disease Activity Index 2000 score and/or a change or increase in therapy. Results Overall, 9/82(11%) patients had flares during follow-up and had lower baseline hydroxychloroquine blood levels than those without flares (220.4 (53.5–1471.1) vs. 1006.3 (53.5–2137.8) ng/ml, p = 0.013). The hydroxychloroquine blood level cut-off that best predicted flares was 613.5 ng/ml (odds ratio = 8.67, 95% confidence interval: 1.66–45.18, p = 0.006). For 77 (94%) patients, the 7-month hydroxychloroquine level dynamics was evaluated and revealed: 59/77 (77%) had a persistent pattern of adequate (41/77(53%)) or fluctuating (18/77 (23%)) levels, with a low and comparable risk of flares (2/41 (5%) vs. 1/18 (5%), p = 1.000). The remaining group had persistent low levels (18/77 (23%)) and their flare frequency was significantly higher than the adequate group (5/18 (28%) vs. 2/41 (5%), p = 0.023). The frequencies of adequate/inadequate hydroxychloroquine blood levels in patients were comparable at baseline and 7 months (McNemar’s test, p = 0.480). Conclusion We provide novel evidence that hydroxychloroquine blood-level patterns (persistently low, adequate, or intermittent) have distinct impacts on flare rates in lupus nephritis patients. These findings reinforce the need of routine hydroxychloroquine measurements to maintain the appropriate blood levels.

Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Objective Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN). Methods Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry. Results There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0–8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6–980.3) vs. 1061.9 (534.8–1590.0 ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013). Conclusions We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0–5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.

ObjectiveTo evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA).MethodsThis was a single-centre, prospective, randomised, investigator-blinded, intervention study (NCT04754698, CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) ≤10, prednisone ≤7.5 mg/day) randomised (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28 and D69. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI >10) and did not withdraw MTX twice.ResultsRandomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group. Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%), p=0.848) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI >10 at D28. At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%), p=0.019), with parallel augmentation in GMT (34.2 (25.2–46.4) vs 16.8 (11.9–23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI >10 was more frequent in MTX-hold at D69 (p=0.024).ConclusionWe provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.

Made available in DSpace on 2022-04-29T08:46:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Objective: To evaluate if the 2019-European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria at diagnosis of childhood-onset systemic lupus erythematosus (cSLE) are associated with higher rates of early damage scored by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). Methods: This retrospective multicenter study included 670 cSLE patients with ≤5 years of disease duration. All patients fulfilled both 2019-EULAR/ACR and 1997-ACR classification criteria. Total score of 2019-EULAR/ACR criteria and each of its specific domains were assessed at diagnosis as predictors of damage accrual at the last visit, according to the presence of any organ damage (defined by SDI ≥ 1). Results: Median disease duration was 2.8 (IQR 1.8–3.8) years and 200 (29.9%) patients had at least one organ damage (SDI ≥ 1). The most frequent domains were neuropsychiatric (12%), renal (7%), and musculoskeletal (6%). There was a higher frequency of renal (58% vs 43%, p = 0.0004) and neuropsychiatric domain (21% vs 7%, p < 0.0001) of 2019-EULAR/ACR criteria in patients with damage (SDI ≥ 1) compared to those without damage (SDI = 0). Patients scoring renal or neuropsychiatric domains of the 2019-EULAR/ACR criteria at diagnosis were associated with renal damage (odds ratio 9.701, 95% confidence interval 3.773–24.941, p < 0.001) or neuropsychiatric damage (OR 9.480, 95% CI 5.481–16.399, p25 was associated with more overall (SDI ≥ 1) (38% vs 25%, p = 0.0002) and renal damage (11% vs 5%, p = 0.023). Conclusions: The 2019-EULAR/ACR criteria at diagnosis were associated with a higher rate of early damage in cSLE patients, especially for renal and neuropsychiatric damage. Of note, damage was particularly associated with high disease activity at diagnosis and 2019-EULAR/ACR score >25. Pediatric Rheumatology Unit Children’s Institute Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Division of Rheumatology Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Pediatric Rheumatology Unit Universidade Federal de Sao Paulo Pediatric Rheumatology Division Sao Paulo State University (UNESP) Pediatric Rheumatology Unit Janeiro Federal University (IPPMG-UFRJ) Pediatric Rheumatology Unit Hospital da Criança de Brasília Jose Alencar Post-graduation Program in Medical Science and Rheumatology Unit University of Brasilia Pediatric Rheumatology Unit Ribeirao Preto Medical School University of Sao Paulo Pediatric Rheumatology Unit Hospital Geral de Fortaleza Pediatric Rheumatology Unit University of Campinas (UNICAMP) Pediatric Rheumatology Unit Pedro Ernesto University Hospital Pediatric Rheumatology Unit Irmandade da Santa Casa de Misericórdia de Sao Paulo Rheumatology Division - Universidade Federal do Rio de Janeiro Hospital Universitário Clementino Fraga Filho Pediatric Rheumatology Unit Federal University of Pará Pediatric Rheumatology Unit Federal University of Bahia Pediatric Rheumatology Unit Hospital Menino Jesus Pediatric Rheumatology Unit Federal University of Pernambuco Pediatric Rheumatology Unit Federal University of Mato Grosso do Sul Pediatric Rheumatology Division Sao Paulo State University (UNESP)

ObjectivesTo evaluate the distinct impact of disease modifying antirheumatic drugs (DMARD) combination and monotherapy in immune response to an inactivated SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA).MethodsThis phase 4 prospective study analysed seroconversion (SC) of anti-SARS-CoV-2 immunoglobulin G (IgG) and neutralising antibodies (NAb) induced by the inactivated vaccine (CoronaVac) in patients with RA in comparison to controls (CG). Disease activity and treatment were also assessed. Only participants with baseline negative IgG/NAb were included.ResultsPatients with RA (N=260) and CG (N=104) had comparable median ages (59 years (50–65 years) vs 58 years (49.8–64 years), p=0.483). Patients with RA had moderate but lower SC (61.8% vs 94.2%, p0.05). After multivariate analyses, factors independently related to reduced SC were: older age (OR=0.79 (0.70–0.89) for each 5-year interval, p7.5 mg/day (OR=0.38 (0.19–0.74), p=0.004) were negatively related to the presence of NAb. Further comparison of SC/NAb positivity among RA treatment subgroups and CG revealed that methotrexate/tofacitinib/abatacept/tocilizumab use, in monotherapy or in combination, resulted in lower responses (pConclusionsPatients with RA under DMARD have a moderate immunogenicity to CoronaVac. We identified that nearly all DMARD combinations have a deleterious effect in immunogenicity, whereas a more restricted number of drugs (methotrexate/tofacitinib/abatacept/tocilizumab) also hampered this response as monotherapy. These findings reinforce the need of a broader approach, not limited to specific drugs, to improve vaccine response for this population.Trial registration detailsNCT04754698.

There is no study specifically focused on SARS-CoV-2 vaccine in primary Sjögren's syndrome (pSS).To assess the immunogenicity, safety, possible effects on disease activity, and autoantibody profile of the Sinovac-CoronaVac vaccine in pSS.Fifty-one pSS patients and 102 sex- and age-balanced controls without autoimmune diseases were included in a prospective phase 4 trial of the Sinovac-CoronaVac vaccine (two doses 28 days apart, D0/D28). Participants were assessed in three face-to-face visits (D0/D28 and six weeks after the 2nd dose (D69)) regarding adverse effects; clinical EULAR Sjögren's Syndrome Disease Activity Index (clinESSDAI); anti-SARS-CoV-2 S1/S2 IgG (seroconversion (SC) and geometric mean titers (GMT)); neutralizing antibodies (NAb); and pSS autoantibody profile.Patients and controls had comparable female sex frequency (98.0% vs. 98.0%, p = 1.000) and mean age (53.5 ± 11.7 vs. 53.4 ± 11.4 years, p = 0.924), respectively. On D69, pSS patients presented moderate SC (67.5% vs. 93.0%, p 0.001) and GMT (22.5 (95% CI 14.6-34.5) vs. 59.6 (95% CI 51.1-69.4) AU/mL, p 0.001) of anti-SARS-CoV-2 S1/S2 IgG but lower than controls, and also, moderate NAb frequency (52.5% vs. 73.3%, p = 0.021) but lower than controls. Median neutralizing activity on D69 was comparable in pSS (58.6% (IQR 43.7-63.6)) and controls (64% (IQR 46.4-81.1)) (p = 0.219). Adverse events were mild. clinESSDAI and anti-Ro(SS-A)/anti-La(SS-B) levels were stable throughout the study (p 0.05).Sinovac-CoronaVac vaccine is safe in pSS, without a deleterious impact on disease activity, and has a moderate short-term humoral response, though lower than controls. Thus, a booster dose needs to be studied in these patients.ClinicalTrials.gov Identifier: NCT04754698. Key Points • Sinovac-CoronaVac vaccine is safe in pSS, without a detrimental effect on systemic disease activity, and has a moderate short-term humoral response • A booster dose should be considered in these patients.

Background: Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). The recent reports of thrombosis associated with the adenovirus-based vaccines raises concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger a dysregulated immune response with possible clotting complications. Therefore, the objectives of this study were to assess immunogenicity, aPL production and safety of Sinovac-Coronavac in PAPS patients.Methods: This prospective controlled phase 4 study of SARS-CoV-2-naïve PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69. Safety and aPL production were also assessed. Results: Forty-four PAPS patients and 132 CG had comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092) and GMT [50.2(95%CI 34.5-73.2) vs. 61.7 (95%CI 52.8-72.3), p=0.249] as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity [64.3% (49.0-77.0) vs. 60.9% (45.6-81.3), p=0.689]. Of note, for D28, the antibody response was very low and also similar in both groups SC (25.8% vs. 30.6% p=0.609). Antiphospholipid levels remained stable throughout the study at D0 vs D28 vs D69 (IgG aCL, p=0.058; IgM aCL, p=0.091; IgG aβ2GPI, p=0.513 and IgM aβ2GPI, p=0.468). Thrombotic event up to 6 months or other moderate/severe side effects were not observed.Conclusions: We provide novel evidence that Sinovac-CoronaVac vaccine has a high immunogenicity and excellent safety profile in PAPS. We further demonstrated that this vaccine did not trigger thrombosis or induced changes in aPL-related antibodies production. Our findings strongly support the recommendation of SARS-CoV-2 vaccination for PAPS patients.Trial registration: ClinicalTrials.gov - Identifier: NCT04754698 first registered on February 8th, 2021.

To evaluate the clinical relevance of high-resolution hand and wrist ultrasound (US) findings and their possible associations with anti-citrullinated peptide antibodies in primary Sjögren's syndrome (pSS).Ninety-seven consecutive pSS patients (American-European Consensus Group, 2002) without meeting the American College of Rheumatology (ACR) criteria (1987) for rheumatoid arthritis (RA); 20 RA patients (ACR/European League Against Rheumatism (EULAR) criteria, 2010); and 80 healthy individuals with comparable age, gender, and ethnicity were enrolled in a case-control study. Disease activity was assessed by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). US was performed by one expert blinded to anti-CCP, anti-MCV, and IgM rheumatoid factor tested by ELISA.Frequencies of grade 3 synovitis (9.3 vs. 0%, p = 0.004), tenosynovitis (36.1 vs. 3.8%, p 0.001), and erosions (27.8 vs. 7.5%, p = 0.001) on US were higher in pSS patients than in healthy controls. ESSDAI presented a moderate correlation with the synovitis number (p = 0.001) and tenosynovitis (p 0.001). Most pSS patients with erosions on US (81.5%) had negative anti-CCP. Nevertheless, anti-CCP ≥ 3× cut-off value was associated with the presence of erosions in pSS (p = 0.026). Erosions in pSS were mainly small size contrasting with moderate/large size in RA (p 0.001), and positive power Doppler synovitis predominated in RA (p 0.001).US identified significant frequencies of grade 3 synovitis, tenosynovitis, and erosions in pSS. Synovitis and tenosynovitis numbers were correlated with ESSDAI. Association between erosions on US and anti-CCP (high titers) in pSS possibly identifies a subgroup with severe arthritis. These findings suggest that US is a useful method for assessing joint involvement in pSS.Key Points• US identified significant frequencies of grade 3 synovitis, tenosynovitis, and erosions in pSS patients in comparison with age- and race-healthy individuals.• Numbers of synovitis and tenosynovitis on US were correlated with ESSDAI values.• Most pSS patients with erosions on US were negative for anti-CCP, but anti-CCP ≥ 3× cut-off value was associated with the presence of erosions in this disease.• Erosions in pSS were mainly small size contrasting with moderate/large size in RA, and positive power Doppler synovitis predominated in RA.

International audience; Objective. Juvenile Sjögren's syndrome (SS) is a rare, poorly defined, and possibly underdiagnosed condition affecting children and adolescents. The aim of this study was to characterize symptoms and clinical findings of juvenile SS and to explore the clinical application of major salivary gland ultrasonography (SGUS) in patients with juvenile SS. Methods. A cross-sectional multicenter study recruited patients with disease onset until age 18 years (n = 67). Disease characteristics were recorded, and unstimulated whole sialometry and SGUS examination of the parotid and submandibular salivary glands were performed. Results. The female:male ratio was 58:9. The mean age at first symptom was 10.2 years and 12.1 years at diagnosis. Ocular and oral symptoms were noted in 42 of 67 patients (63%) and 53 of 66 patients (80%), respectively. The American-European Consensus Group or American College of Rheumatology/European League Against Rheumatism classification criteria for primary SS were fulfilled by 42 of 67 patients (63%). Pathologic SGUS findings were observed in 41 of 67 patients (61%); 26 of 41 SGUS+ patients (63%) fulfilled primary SS criteria. Salivary gland enlargements/parotitis were noted in 37 of 58 patients and were nonsignificantly associated with SGUS+ status (P = 0.066). The mean levels of saliva were 5.6 ml/15 minutes in SGUS-patients compared to 3.3 ml/15 minutes in the SGUS+ patients (P = 0.049). A total of 36 of 41 SGUS+ patients (88%) were anti-Ro/La+ compared to 14 of 26 SGUS-patients (54%) (P = 0.001). In addition, 24 of 39 SGUS+ patients (62%) were positive for rheumatoid factor (RF), whereas only 5 of 25 SGUS-patients (20%) were RF+ (P = 0.001). Conclusion. Juvenile SS is characterized by a large spectrum of clinical symptoms and findings. Several glandular and extraglandular parameters such as hyposalivation, swollen salivary glands, and autoantibodies are associated with pathologic SGUS findings.

Background Thalidomide has shown exceptional results in systemic/cutaneous lupus erythematosus(SLE/CLE). Recently, lenalidomide has been also prescribed for SLE/CLE treatment. Literature regarding efficacy/adverse events for these drugs is scarce with a single systematic review and meta-analysis focused solely on thalidomide for refractory cutaneous lupus subtypes. Objective We, therefore, addressed in this narrative review the efficacy/adverse effects of thalidomide and lenalidomide for SLE and CLE. In addition, we provide a specialist approach for clinical practice based on the available evidence. Results Efficacy of thalidomide for refractory cutaneous lupus treatment was demonstrated by several studies, mostly retrospective with small sample size(≤20). The frequency of peripheral polyneuropathy is controversial varying from 15-80% with no consistent data regarding cumulative dose and length of use. Drug withdrawn results in clinical partial/complete reversibility for most cases (70%). For lenalidomide, seven studies (small sample sizes) reported its efficacy for SLE/CLE with complete/partial response in all patients with a mean time to response of 3 months. Flare rate varied from 25-75% occurring 0.5-10 months after drug withdrawn. There were no reports of polyneuropathy/worsening of previous thalidomide-induced neuropathy, but most of them did not perform nerve conduction studies. Teratogenicity risk exist for both drugs and strict precautions are required. Conclusions Thalidomide is very efficacious as an induction therapy for patients with severe/refractory cutaneous lupus with high risk of scarring, but its longstanding use should be avoided due to neurotoxicity. Lenalidomide is a promising drug for skin lupus treatment, particularly regarding the apparent lower frequency of nerve side effects.

Introduction Influenza A (H3N2) virus is the most important cause of seasonal influenza morbidity and mortality in the last 50 years, surpassing the impact of H1N1. Data assessing immunogenicity and safety of this virus component are lacking in systemic lupus erythematosus (SLE) and restricted to small reports with other H3N2 strains. Objective This study aims to evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in SLE. Methods 81 consecutive SLE patients and 81 age- and sex-matched healthy controls (HC) were vaccinated with the influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers(GMT), and factor increase in GMT(FI-GMT) and adverse events were assessed before and 4 weeks post-vaccination. Disease activity and therapies were also evaluated. Results Before immunization, SLE and HC groups had high SP rates (89% vs 77%, p = 0.061) and elevated GMT titer with higher levels in SLE (129.1(104.1–154.1) vs 54.8(45.0–64.6), p < 0.001). Frequency of two previous years’ influenza vaccination was high and comparable in SLE and HC (89% vs 90%, p = 1.000). Four weeks post-vaccination, median GMT increased for both groups and remained higher in SLE compared to HC (239.9(189.5–290.4) vs 94.5(72.6–116.4), p < 0.0001) with a comparable FI-GMT (2.3(1.8–2.9) vs 1.9(1.5-2.3), p = 0.051). SC rates were low and comparable for both groups (16% vs 11%, respectively, p = 0.974). Disease activity scores remained stable throughout the study ( p = 1.000) and severe adverse events were not identified. Conclusion Influenza A/Singapore (H3N2) vaccine has an adequate safety profile. The distinct immunogenicity pattern from other influenza A components characterized by a remarkably high pre- and post-vaccination SP rate and high GMT levels may be associated with previous influenza A vaccination. ( www.clinicaltrials.gov , NCT03540823).

Objectives To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities and therapy on immune response. Methods This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titre (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis. Results Patients and CTRL had comparable sex (P>0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL-naïve participants revealed at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P0.05). Conclusion Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. We further identified that immunosuppression is associated with diminished NAb positivity. Trial registration COVID-19 CoronaVac in Patients With Autoimmune Rheumatic Diseases and HIV/AIDS (CoronavRheum), http://clinicaltrials.gov/ct2/show/NCT04754698

Introduction In 2016 the American Academy of Ophthalmology(2016-AAO) recommended a maximum daily HCQ use of 5.0 mg/kg real body weight(RBW) taking into consideration minimizing eye toxicity. Retinopathy in systemic lupus erythematosus(SLE) patients was recently associated with obesity and this condition is progressively more common in these patients. However, the impact of obesity in HCQ blood levels remains controversial. Objective To determine if the 2016-AAO recommendation based on RBW with and without maximum daily dose restriction results in adequate and safe blood levels in obese lupus nephritis(LN) patients. Methods A cross-sectional study was performed with 108 LN patients under the prescribed 2016-AAO dose for at least 3 months. LN patients were assessed for demographic characteristics, body mass index(BMI), disease parameters, HCQ dose, concomitant treatment and HCQ blood levels measured by liquid chromatography-tandem mass spectrometry. Obesity was defined as BMI ≥30kg/m2. Results Obesity was identified in 35/108(32%) LN patients. The calculation of HCQ daily dosage revealed that obese patients were under a lower prescribed daily dose according to the real body weight (RBW) [4.4(2.9-5.4) vs. 4.9(4-5.5)mg/Kg/day, p Conclusion Obese patients under the 2016-AAO prescribed dose of HCQ based on RBW with and without maximum daily dose restriction have a very high HCQ blood levels compared to non-obese patients, with a potential increased risk of ocular toxicity. The use of 2016-AAO dose of HCQ according to the ideal body weight for this group of patients should be considered.Clinicaltrials.gov #NCT0312243.

CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.

Background Brazil faced a yellow fever(YF) outbreak in 2016–2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. Objective This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. Methods and Results A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3–1292.2) vs.731 (95%CI 593.6–900.2), p0.05). Conclusion Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(>80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas. Trial registration This clinical trial was registered with Clinicaltrials.gov (#NCT03430388)., Author summary Yellow fever is a viral hemorragic fever with high mortality rate and the vaccine is a remarkably successful way of preventing it. As a live attenuated virus vaccine, it is not recommended for rheumatic and other immunossupressed patients in general. However, in an outbreak scenario, the risk of dying of the disease can be higher than the risk of a vaccine serious adverse event. In 2018, the fractional-dose yellow fever vaccine was offered to the hospital employees and to the rheumatic patients without or with low immunossupression therapy in Hospital das Clinicas of University of São Paulo, during the yellow fever outbreak in São Paulo, Brazil. In order to optimize the yellow fever vaccine (YFV) supply, the fractional-dose (corresponding to one fifth) was adopted in the public vaccine campaign. This is the first study evaluating the primary vaccination with fractional-dose YFV in autoimmune rheumatic diseases(ARD) patients (n = 159) under low immunosuppression. Most vaccinated participants were able to produce enough neutralizing antibodies to be protected against yellow fever (seroconversion rate of 84% versus 96% in healthy controls). Neither activity of the rheumatic disease or serious adverse event was identified during the 30 days of followup after the vaccination.

Objective To assess the possible effect of therapy, disease subtype and severity on H1N1 immunogenicity in patients with SSc. Methods Ninety-two patients and 92 age- and gender-matched healthy controls received adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Blood samples were collected immediately before and 3 weeks after vaccination to evaluate antibody responses to the H1N1 virus. Efficacy was assessed by seroprotection (SP) and seroconversion (SC) rates and the factor increase in geometric mean antibody titre. Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. Results SSc patients were predominantly females (91%) and 61% had limited SSc, 12% had severe skin involvement and 57.6% were on immunosuppressive (IS) therapy. SSc patients and controls presented comparable overall SP (P = 0.20) and SC (P = 0.61) rates. Further evaluation of the possible effect of disease and therapy revealed similar rates of SP and SC in patients with dcSSc vs lcSSc (SP P = 0.62 and SC P = 0.66), severe vs mild/moderate skin involvement (SP P = 1 and SC P = 0.45) and with vs without IS (SP P = 0.26 and SC P = 0.10). The frequency of mild local and minor systemic reactions was similar in patients with dcSSC vs lcSSc (P = 0.70 vs 0.32) and in those with and without severe skin involvement (P = 0.59 vs 0.28). Conclusion The non-adjuvanted influenza H1N1 virus vaccine proved to be safe and effective, independent of SSc clinical subtype, disease severity or therapy. These latter factors do not seem to contribute to mild adverse events observed in SSc. Our data support the annual influenza vaccination recommendation for these patients. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov), NCT01151644.

Background Primary Sjögren’s syndrome (pSS) is a systemic immune-mediated disease whose main characteristic is exocrine gland inflammation and, subsequent reduction in tear and saliva production. A delayed diagnosis is common due to the nonspecific clinical manifestations of disease. The aim of the present study was to develop recommendations for the diagnosis of glandular manifestations of pSS based on evidence and expert opinion. Main body of the abstract We conducted a systematic literature review to retrieve the best evidence available on the accuracy of diagnostic tests for pSS. We also held two in-person meetings with experts (rheumatologists, pathologists, ophthalmologists and dentists) to establish their level of agreement using the Delphi method. Ultimately, we generated 18 recommendations that aim to facilitate the diagnosis of the glandular manifestations of pSS. Conclusion The diagnosis of glandular manifestations of pSS is complex and multidisciplinary. It requires specific knowledge in the field of ophthalmology, immunology, pathology and imaging, making it compulsory for the rheumatologist to work with professionals from these different areas in order to improve accuracy and early diagnosis. Glandular dysfunction tests, ANA, RF, Anti-Ro, protein electrophoresis, urinalysis, blood count, C-Reactive protein, complement, testing for syphilis and viruses (HCV, HIV) and SGUS should be investigated when dryness or systemic manifestation are present. Minor salivary gland biopsy is recommended for all anti-Ro negative or incomplete criteria cases.

BACKGROUND/OBJECTIVE Our aim was to describe the short- and long-term outcome of peripheral neuropathy (PN) attributed exclusively to systemic lupus erythematosus (SLE). METHODS Systemic lupus erythematosus patients with defined PN (clinical and electroneuromyography) were retrospectively evaluated at onset, 1-year, and 5-year follow-up using a standardized electronic chart database that started in 2000. Exclusion criteria were comorbidities, drugs, and infections. Age-, sex-, and disease duration-matched SLE patients without PN were selected as controls. RESULTS Lupus PN was identified in 38 (1.8%) of 2074 patients, and almost two thirds had PN onset in the first 5 years of SLE (63.2%). Peripheral neuropathy SLE had higher frequencies of cutaneous vasculitis (50% vs 21.1%, p = 0.002), lymphopenia (60.5% vs 36.8%, p = 0.027), anti-Sm (52.6% vs 27.6%, p = 0.013), and higher SLEDAI-2K scores (11.5 ± 10.5 vs 4.9 ± 6.7, p < 0.001) compared with controls. The most common type was polyneuropathy (71.1%) with sensory-motor pattern (68.4%). At PN diagnosis, all patients received glucocorticoid and 97.4% started immunosuppressive therapy (50% intravenous cyclophosphamide, 42.1% azathioprine). After 1-year follow-up, 92.1% had a favorable outcome with complete (36.8%) or partial remission (55.2%), in parallel with a decrease in prednisone dose (48.3 ± 17.9 vs 15.3 ± 13.4 mg/d, p < 0.001), symptomatic therapy (57.9% vs 29.7%, p = 0.02), and SLEDAI-2K score (11.5 ± 10.5 vs 1.7 ± 3.7, p < 0.001). SLEDAI-2K scores were higher in patients who had PN onset with less than 1 year of SLE duration, compared with those with more than 5 years of disease (21.3 ± 9.1 vs 3.9 ± 5.3, p < 0.001). Early-PN-onset group had a better response to treatment (complete remission at 1-year follow-up 61.5% vs 25%, p = 0.039). At 5-year follow-up, 89.3% remained with complete/partial remission. CONCLUSIONS Peripheral neuropathy attributed to SLE itself is a rare manifestation with a bimodal pattern, characterized by a predominant early-onset group associated with high disease activity and a higher rate of complete remission, and a late-onset group with low disease activity and a partial therapy response.

Background: The V Brazilian Consensus for determination of autoantibodies against cellular constituents on HEp-2 cells, held in Brasilia (DF, Brazil) on August 27, 2016, discussed the harmonization between the Brazilian Consensus on ANA (BCA) guidelines and the International Consensus on ANA Patterns (ICAP) recommendations (www.anapatterns.org). Initial guidelines were formulated by the group of Brazilian experts with the purpose of guiding and enabling Brazilian clinical laboratories to adopt recommendations and to provide a common standard for national and international consensuses. Mainbody: Twenty Brazilian researchers and experts from universities and clinical laboratories representing the various geographical regions of the country participated in the meeting. Three main topics were discussed, namely the harmonization between the BCA guidelines and latest recommendations of the ICAP initiative, the adjustment of the terminology and report on HEp-2 patterns, and a reassessment of quality assurance parameters. For the three topics, our aim was to establish specific guidelines. All recommendations were based on consensus among participants. There was concrete progress in the adjustment of the BCA guidelines to match the ICAP guidelines. To a certain extent, this derives from the fact that ICAP recommendations were largely based on the algorithm and recommendations of the IV Brazilian ANA Consensus, as consistently recognized in the ICAP publications and presentations. However, although there is great overlap between the two Consensuses, there are some point divergences. These specific items were individually and extensively discussed, and it was acknowledged that in several points ICAP improved recommendations previously issued by the Brazilian ANA Consensus and these changes were readily implemented. Regarding some specific topics, the BCA panel of experts felt that the previously issued recommendations remained relevant and possibly will require further discussion with ICAP. The term anti-cell antibodies was adopted as the recommended designation, recognizing that the assay addresses antibodies against antigens in the nucleus and in other cell compartments. However, the acronym ANA HEp-2 was maintained due to historical and regulatory reasons. It was also signalized that the latest trend in ICAP is to adopt the term Indirect Immunofluorescent Assay on HEp-2 cell substrate (HEp-2 IIFA). In addition, the quality assurance strategies previously presented were ratified and emphasized. Conclusion: The V BCA edition was successful in establishing an overall harmonization with the ICAP recommendations for interpretation of the HEp-2 IIFA test, pinpointing the perspectives in filling the remaining gaps between both initiatives.

To assess the longitudinal production of anti-adalimumab antibody (AAA) and baseline risk factors for this antibody development in juvenile idiopathic arthritis (JIA) patients initiating adalimumab (ADA).Thirty consecutive JIA patients under ADA therapy were prospectively followed. JIA clinical/laboratorial/treatment data and sera for ADA and AAA assays (ELISA and bridging ELISA) were obtained at baseline (BL), 2 months (2M), 3 months (3M), 6 months (6M), 12 months (12M), and 24 months (24M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels).AAA was absent at BL, first detected at 2M after ADA initiation in 2/30 (7%) patients with a significant increase at 3M (10/29 (34%), p = 0.013) and no major change in 6M (11/30 (37%)) and 12M (9/26 (35%)). Of note, at 3M, AAA levels correlated negatively with ADA levels (r = - 0.781, p = 0.0001). Analysis of BL predictors revealed a significantly higher risk of developing AAA in patients with female gender (OR 21; 95% CI 1.08-406.57; p = 0.044), ESR30 mm/1st hour (OR 5.44; 95% CI 1.04-28.53; p = 0.045), and leflunomide use (OR 9.33; 95% CI 1.51-57.66; p = 0.016). In contrast, concomitant use of methotrexate was protective for AAA appearance (OR 0.08; 95% CI 0.01-0.53; p = 0.009). After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared with 15% in AAA-negative group (p = 0.03).This study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 24M. We also identified female gender, increased ESR, and leflunomide use as relevant risk factors for AAA production at BL, whereas methotrexate was protective. Early systematic monitoring of AAA at 3M may, therefore, guide drug switching in these patients.Key Points• Anti-adalimumab antibodies (AAA) production kinetics demonstrated a timely significant increase starting at 3M in juvenile idiopathic arthritis (JIA) patients under adalimumab therapy• Female gender, increased ESR, and leflunomide use were identified as relevant risk factors for AAA production in JIA, whereas methotrexate was protective.

OBJECTIVES To evaluate volumetric BMD (vBMD), microarchitecture and strength and vertebral fractures (VFs) in primary SS (pSS). METHODS We evaluated 71 female pSS patients and 71 gender-, age-, and race-matched controls. Clinical data including risk factors for osteoporosis (OP) and fractures were collected through a standardized protocol. Areal BMD and VFs were analysed by DXA. Bone microarchitecture, vBMD and bone strength were assessed by high-resolution peripheral quantitative CT (HR-pQCT), a non-invasive method. RESULTS pSS patients and controls were comparable for age, BMI, calcium intake, smoking, menopause, sedentary lifestyle and family history of fractures (P > 0.05). OP or low BMD for the patient's age (33.8 vs 5.6%; P < 0.0001) and VFs (19.7 vs 5.6%; P = 0.043) were more frequent in patients than controls. HR-pQCT showed deterioration of cortical and trabecular components and strength at the radius, and of cortical components and strength at the tibia (P < 0.05) in patients compared with controls. pSS patients and controls were also analysed by multivariate analysis adjusted for age, ethnicity, prednisone use, weight and height, which showed that the pSS group had lower values of cortical vBMD, cortical thickness and apparent modulus (P < 0.05) at the radius and cortical vBMD and apparent modulus (P < 0.05) at the tibia. Patients with VFs had more cortical bone deterioration (cortical vBMD/cortical thickness) at the tibia compared with patients without VFs (P < 0.05). CONCLUSIONS This study was the first to assess bone microarchitecture in pSS and demonstrated that cortical deterioration is the most important abnormality observed in pSS patients with VFs. This novel finding shows that this compartment contributes to vertebral fragility, suggesting that this non-invasive evaluation may be useful in the clinical practice.

African-Brazilians comprise a group of blacks and "pardos." As racial differences can be associated with distinct presentations, we evaluated the clinical and serological associations of African-Brazilians with systemic sclerosis (SSc).Sera from 260 adult SSc patients (203 whites and 57 African-Brazilians) were evaluated. Patients with overlap syndromes were excluded. Clinical and demographic data were obtained from an electronic register database. Laboratory analysis included the following: anti-CENP-A/CENP-B, Scl70, RNA polymerase III, Ku, fibrillarin, Th/To, PM-Scl75, and PM-Scl100 by line immunoassay and anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cells.African-Brazilian SSc patients presented shorter disease duration (12.8 ± 6.5 vs. 15.9 ± 8.1 years, p = 0.009), higher frequency of nucleolar ANA pattern (28% vs. 13%, p = 0.008), and lower frequencies of centromeric ANA pattern (14% vs. 29%, p = 0.026) and CENP-B (18% vs. 34%, p = 0.017), as well as an association with severe interstitial lung disease (58% vs. 43%; p = 0.044). Further comparison of ethnic groups according to subsets revealed that diffuse SSc African-Brazilian patients presented higher frequency of pulmonary hypertension (p = 0.017), heart involvement (p = 0.037), nucleolar ANA pattern (p = 0.036), anti-fibrillarin antibodies (p = 0.037), and higher mortality (48% vs. 19%; p = 0.009). A different pattern was observed for the limited subset with solely a lower frequency of esophageal involvement (p = 0.050) and centromeric ANA pattern (p = 0.049). Survival analysis showed that African-Brazilians had a higher mortality, when adjusted for age, gender, and clinical subset (RR 2.06, CI 95% 1.10-3.83, p = 0.023).African-Brazilians have distinct characteristics according to clinical subset and an overall more severe SSc than whites, similar to the blacks from other countries.Key Points • African-Brazilian SSc patients were associated with severe interstitial lung disease and nucleolar ANA pattern when compared to white SSc patients. • When disease subsets were considered, African-Brazilian patients with diffuse SSc presented association with pulmonary hypertension, heart involvement, nucleolar ANA pattern, and anti-fibrillarin antibodies. • White SSc patients were associated with centromeric ANA pattern. • Survival analysis at 5, 10, 15, and 20 years, adjusted for age, gender, and disease subset, was significantly worse in African-Brazilian SSc patients.

Background and objective Primary Sjogren syndrome (pSS) is a systemic autoimmune rheumatic disease that particularly affects exocrine glands. Dry eye is one of the most important features of this syndrome, and a recent study reported reduced deoxyribonuclease I (DNase I) activity in the tear of patients with dry eye. We therefore postulated that patients with pSS might have antibodies targeting DNAse I. Methods We have evaluated in a cross-sectional study 85 patients with pSS (2002 American-European Consensus Group Criteria), 50 rheumatoid arthritis (RA) patients (1987 American College of Rheumatology Criteria) without sicca symptoms, and 88 healthy volunteers. IgG anti-DNase I was detected by enzyme-linked immunosorbent assay using as antigen bovine pancreas enzyme and confirmed by immunoblotting. Results Age and sex were alike in the 3 groups (p > 0.05). Anti-DNase I was detected in 43.5% of the pSS patients. In contrast, this reactivity was absent in all RA patients (p = 0.0001). Additional comparison of pSS patients with (n = 37) or without (n = 48) anti-DNase I showed that the former group had higher IgG serum levels (2293.2 ± 666.2 vs 1483.9 ± 384.6 mg/dL, p = 0.0001) and greater rate of non-drug-induced leukopenia (43% vs 19%, p = 0.02). A multivariate logistic regression analysis identified that only IgG levels were independently associated with anti-DNase I. Conclusions We describe a high frequency of anti-DNase I antibodies in pSS patients associated with higher serum IgG levels. The lack of this reactivity in RA patients without sicca symptoms suggests that this antibody may be helpful in the differential diagnosis of these diseases.

The recommendations proposed by the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology for the treatment of Sjögren's syndrome were based on a systematic review of literature in Medline (PubMed) and the Cochrane databases until October 2014 and on expert opinion in the absence of studies on the subject. 131 articles classified according to Oxford & Grade were included. These recommendations were developed in order to guide the management and facilitate the access to treatment for those patients with an appropriate indication, considering the Brazilian socioeconomic context and pharmacological agents available in this country.

OBJECTIVE: To determine the prevalence of sicca symptoms, dry eye, and secondary Sjögren's syndrome and to evaluate the severity of dry eye in patients with mixed connective tissue disease. METHODS: In total, 44 consecutive patients with mixed connective tissue disease (Kasukawa's criteria) and 41 healthy controls underwent Schirmer's test, a tear film breakup time test, and ocular surface staining to investigate dry eye. In addition, the dry eye severity was graded. Ocular and oral symptoms were assessed using a structured questionnaire. Salivary gland scintigraphy was performed in all patients. Classification of secondary Sjögren's syndrome was assessed according to the American-European Consensus Group criteria. RESULTS: The patients and controls had comparable ages (44.7±12.4 vs. 47.2±12.2 years) and frequencies of female gender (93 vs. 95%) and Caucasian ethnicity (71.4 vs. 85%). Ocular symptoms (47.7 vs. 24.4%) and oral symptoms (52.3 vs. 9.7%) were significantly more frequent in patients than in controls. Fourteen (31.8%) patients fulfilled Sjögren's syndrome criteria, seven of whom (50%) did not have this diagnosis prior to study inclusion. A further comparison of patients with mixed connective tissue disease with or without Sjögren's syndrome revealed that the former presented significantly lower frequencies of polyarthritis and cutaneous involvement than did the patients without Sjögren's syndrome. Moderate to severe dry eye was found in 13 of 14 patients with mixed connective tissue disease and Sjögren's syndrome (92.8%). CONCLUSIONS: Sjögren's syndrome, particularly with moderate to severe dry eye, is frequent in patients with mixed connective tissue disease. These findings alert the physician regarding the importance of the appropriate diagnosis of this syndrome in such patients.

The aim of this longitudinal prospective study was to evaluate the effects of periodontal treatment on the clinical, microbiological and immunological periodontal parameters, and on the systemic activity (ESSDAI) and subjective (ESSPRI) indexes in patients with primary Sjögren’s Syndrome (pSS). Twenty-eight female patients were divided into four groups: pSS patients with or without chronic periodontitis (SCP, SC, respectively), and systemically healthy patients with or without chronic periodontitis (CP, C, respectively). Periodontal clinical examination and immunological and microbiological sample collection were performed at baseline, 30 and 90 days after nonsurgical periodontal treatment (NSPT). Levels of interleukin IL-1β, IL-8 and IL-10 in saliva and gingival crevicular fluid (GCF) were evaluated by ELISA, as well as the expression of Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans, (Aa) Tannerella forsythia (Tf), and Treponema denticola (Td), by qPCR. Systemic activity and pSS symptoms were evaluated by ESSDAI and ESSPRI. NSPT resulted in improved periodontal clinical parameters in both SCP and CP groups (p>0.05). Pg, Aa, and Tf levels decreased after NSPT only in CP patients (p

ObjectiveThe objectives of this paper are to objectively measure habitual physical activity levels in patients with primary Sjögren’s syndrome (pSS) with mild disease activity and to determine to which extent it may be associated with physical capacity and function and clinical features.MethodsIn this cross-sectional study, 29 women with pSS were objectively assessed for habitual physical activity levels (using accelerometry) and compared with 20 healthy women (CTRL) frequency-matched for physical activity levels, age, body mass index, and body fat percentage with regard to physical capacity and function, fatigue, depression, pain, and health-related quality of life.ResultspSS showed 8.5 min/day of moderate-to-vigorous physical activity (MVPA) when only MVPA accumulated in bouts ≥ 10 min was considered; when considering total MVPA (including bouts 2peak, lower muscle strength and function, higher fatigue, and poorer health-related quality of life when compared with CTRL ( p ConclusionWhen compared to physical activity-matched healthy controls, pSS patients showed reduced physical capacity and function, increased fatigue and pain, and reduced health-related quality of life. Except for aerobic conditioning, these differences were sustained when only more physically active participants were compared, indicating that minimum recommended levels of physical activity for the general population may not be sufficient to counteract pSS comorbidities.

Antibody to Epstein–Barr virus (EBV) early antigen diffuse (anti-EA-D) is associated with viral replication. However, their possible associations with clinical/therapeutic features in primary Sjogren’s syndrome (pSS) were not established. We evaluated 100 pSS patients (American–European Criteria) and 89 age/gender/ethnicity-matched healthy controls. Disease activity was measured by EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI). Antibodies to EBV (anti-VCA IgG/IgM, anti-EBNA-1 IgG, anti-EA-D IgG) were determined by ELISA. Patients and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs. 86.5 %, p = 0.501; 2.6 ± 1.1 vs. 2.5 ± 1.1 AU/mL, p = 0.737) and anti-EBNA-1 IgG (92 vs. 94.4 %, p = 0.576; 141.3 ± 69.8 vs. 135.6 ± 67.5 RU/mL, p = 0.464). Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and increased mean levels of anti-EA-D were observed in patients than controls (36 vs. 4.5 %, p < 0.0001; 38.6 ± 57.4 vs. 7.9 ± 26.3 RU/mL, p < 0.0001). Further analysis of patients with (n = 36) and without (n = 64) anti-EA-D revealed comparable age/gender/ethnicity (p ≥ 0.551), current prednisone dose (4.8 ± 6.9 vs. 5.1 ± 10.4 mg/day, p = 0.319), and current uses of prednisone (52.8 vs. 37.5 %, p = 0.148) and immunosuppressants (44.4 vs. 31.3 %, p = 0.201). ESSDAI values were comparable (p = 0.102), but joint activity was more frequent (25 vs. 9.4 %, p = 0.045) in anti-EA-D positive patients. Anti-EA-D antibodies were not associated with anti-Ro/SSA (p = 1.000), anti-La/SSB (p = 0.652), rheumatoid factor (p = 1.000), anti-α-fodrin (p = 0.390) or antiphospholipid antibodies (p = 0.573), not suggesting cross-reactivity. The higher anti-EA-D frequency associated with joint activity raises the possibility that a subclinical EBV reactivation may trigger or perpetuate the articular involvement in pSS.

Antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) have been described in primary Sjogren’s syndrome (pSS) with controversial findings regarding aPL prevalence and their association with thrombotic events. We evaluated 100 consecutive pSS patients (American–European criteria) and 89 age–gender–ethnicity-matched healthy controls for IgG/IgM anticardiolipin (aCL), IgG/IgM anti-beta2-glycoprotein-I (aβ2GPI), and lupus anticoagulant (LA) (positivity according to APS Sydney’s criteria). Clinical analysis followed standardized interview and physical examination assessing thrombotic and nonthrombotic APS manifestations and thrombosis risk factors. aPLs were detected in 16 % patients and 5.6 % controls (p = 0.035). LA was the most common aPL in patients (9 %), followed by aβ2GPI (5 %) and aCL (4 %). Thrombotic events occurred in five patients [stroke in two, myocardial infarction in one and deep-vein thrombosis (DVT) in four], but in none of controls (p = 0.061). Mean age at time of stroke was 35 years. Three patients with thrombotic events (including the two with stroke) had APS (Sydney’s criteria) and were positive exclusively for LA. Comparison of patients with (n = 16) and without (n = 84) aPL revealed similar mean age, female predominance, and ethnicity (p > =0.387). Frequencies of livedo reticularis (25 vs. 4.8 %, p = 0.021), stroke (12.5 vs. 0 %, p = 0.024), and DVT (18.8 vs. 1.2 %, p = 0.013) were significantly higher in APL + patients. Conversely, frequencies of hypertension, dyslipidemia, diabetes, obesity, smoking, sedentarism, and hormonal contraception were similar in patients with or without aPL (p ≥ 0.253). Our study identified LA as an important marker for APS in pSS, particularly for stroke in young patients, warranting routine evaluation of these antibodies and rigorous intervention in modifiable risk factors.

The objective of the study was to evaluate risk factors for pulmonary tuberculosis in systemic lupus erythematosus (SLE). Clinical/laboratorial features of 1283 SLE patients (ACR criteria) followed at the Lupus Clinic were obtained from the electronic register database from 2001 to 2009. Pulmonary tuberculosis was diagnosed in 20 patients (1.6%) (TB+ group). As control group (TB-), 40 patients without tuberculosis matched for age, gender, ethnicity, age at SLE diagnosis, and disease duration were arbitrarily selected. All 20 patients of the TB+ group presented confirmed pulmonary tuberculosis from 1 to 23 years after SLE diagnosis (7.6 ± 8.1 years). Frequencies of previous SLE involvements (cutaneous, articular, hematological, renal, pericarditis, pneumonitis, and central nervous system) were alike in TB+ and TB- groups (p > 0.05). In contrast, prior pleuritis was more frequent in the TB+ group (40% vs. 5%, p = 0.001). In fact, pulmonary tuberculosis was diagnosed in 8/10 patients with previous pleuritis. Immunosuppressive and corticosteroid therapies at the moment of tuberculosis diagnosis were also similar in both groups (p > 0.05). We have identified pleuritis as a relevant risk factor for pulmonary tuberculosis, suggesting that previous pleural injury is a critical part of the complex interplay between altered immune system, socio-economic conditions, and increased susceptibility to this mycobacterial infection.

Metabolic syndrome (MetS) has been described in autoimmune diseases. However, there are scarce data about MetS and adipocytokine profile in primary Sjogren's syndrome (pSS). Seventy-one female pSS patients (American-European Consensus Group Criteria, 2002) aged 18-65 years and 71 age-, race-matched control women were enrolled in this case-control study. Clinical data were collected by a standardized protocol. Blood levels of glucose, cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, interleukin-1beta (IL-1beta)/IL-6, B-cell activating factor (BAFF), insulin, and leptin/adiponectin/visfatin/resistin were determined. Patients and controls were comparable regarding body mass index (BMI), smoking, sedentariness, and menopause (p > 0.05). MetS (39.4 vs. 16.9 %, p = 0.005), hypertension (p = 0.004), and dyslipidemia (p = 0.002) were more frequent in patients than controls. IL-1beta, IL-6, BAFF, resistin, and adiponectin levels were higher in patients than controls (p

Herpes zoster infection was significantly more often observed in children (10%, N = 362) than in adults (4%, N = 1830). At herpes zoster infection diagnosis, disease activity score (8 vs. 3, P = 0.002) was higher in children, and fever (43% vs. 12%, P < 0.0001), nephritis (45% vs. 25%, P = 0.038), anti-double-stranded DNA autoantibodies (76% vs. 15%, P < 0.0001) and low C4 (48% vs. 22%, P = 0.017) were more often observed in children versus adults. Post herpetic neuralgia was less common in children than adults (3% vs. 24%, P =0.005).

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect multiple organs and thus has a large spectrum of clinical presentations. Assessment of the autoantibody profile is fundamental for the clinical management of SLE patients, providing important data for diagnosis, clinical characterization and disease activity evaluation. Anti-ribosomal P protein (anti-Rib-P, anti-P) antibody, described in the 1980s, is a serological marker for SLE that is present in 13-20% of cases. This reactivity was initially thought to be associated with neuropsychiatric involvement in SLE, with certain conflicting results. Subsequently, associations of anti-Rib-P with liver and renal involvement in lupus were reported. Recently, anti-Rib-P was detected in autoimmune hepatitis patients. Anti-Rib-P reactivity to Trypanosoma cruzi ribosomal target antigens in patients with Chagas heart disease has also been described. This review focuses on the usefulness of the determination of anti-Rib-P in SLE and in other autoimmune and non-autoimmune disorders in clinical practice.

To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE).Fifty-seven adult c-SLE female patients and 21 healthy controls were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Müllerian hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual abnormalities, disease activity, damage, and treatment were also analysed.The median current age was similar in adult c-SLE patients and controls (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p = 0.037) and AFC (6 vs. 16, p0.001) were significantly reduced in SLE patients compared to controls without significant menstrual abnormalities. Anti-CoL were solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated with demographic data, ovarian reserve parameters, disease activity/damage, and treatment. Further evaluation of c-SLE patients treated with cyclophosphamide revealed a higher median of FSH levels compared to c-SLE patients not treated with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs. 16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with methotrexate demonstrated a negative correlation between the cumulative dose and AMH levels (p = 0.027, r = -0.507).The present study demonstrated for the first time that a high cumulative methotrexate dose is a possible cause of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are required to confirm this deleterious effect in other rheumatic diseases, particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.

To provide an update on infections in systemic lupus erythematosus (SLE) and Sjögren's syndrome, particularly addressing their role as triggers of autoimmunity, their impact on mortality, the main microorganisms, the approaches to differential diagnosis with disease flares and recommendations for vaccination.New mechanisms for autoimmunity triggered by Epstein-Barr virus and human commensal microbiota have been described. The increased risk for tuberculosis was recently demonstrated for the first time in Sjögren's syndrome. C-reactive protein was reported to be a more sensitive and specific marker for bacterial infections in SLE than procalcitonin and phagocyte-specific S100A8/A9 protein. Inactivated vaccines are well tolerated and efficacy was demonstrated for influenza vaccine. Immunogenicity is generally reduced but adequate in SLE. Prednisone or immunosuppressants are associated with decreased vaccine serological response, whereas hydroxicloroquine seems to improve vaccine immunogenicity. Other infection-preventive measures for these diseases include antimalarials and prophylaxis for tuberculosis or Pneumocystis jirovecii.Advances in the role of infectious agents as triggers for SLE and Sjögren's syndrome have provided new insights into disease development. Knowledge on vaccine immunogenicity, safety and efficacy has improved with evidence of a generally reduced but adequate response for inactivated vaccines in SLE. Other preventive measures comprise infection prophylaxis and antimalarials.

Objective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) 520 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED 520 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED 520 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED 520 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED 520 mg + IS + CQ (57.4%; P = 0.09). Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644.

Objectives. To evaluate the frequency of seizures in primary antiphospholipid syndrome (PAPS) and their possible clinical and laboratory associations.Methods. Eighty-eight PAPS patients (Sydney’s criteria) were analyzed by a standard interview, physical examination and review of medical charts. Risk factors for seizures, clinical manifestations, associated comorbidities, and antiphospholipid antibodies were evaluated.Results. Nine (10.2%) patients with seizures were identified, 77.8% had convulsions onset after PAPS diagnosis. Mean age, gender, and race were comparable in groups with or without seizures. Interestingly, a higher frequency of current smoking (44.4 versus 10.1%, ) was observed in the first group. Stroke, Sneddon’s syndrome, and livedo reticularis were more frequent in PAPS patients with seizures than those without seizures, although not statistically significant (). Comparison between patients with seizures onset after PAPS diagnosis () and those without convulsions () demonstrated a higher frequency of current smoking (42.9 versus 10%, ) and stroke in the first group (71.4 versus 30.4%, ). Regression analysis confirmed that smoking () and stroke () were independently associated to seizures.Conclusion. About 10.2% of PAPS patients had convulsions, predominantly after PAPS diagnosis, and seizures were associated to current smoking and stroke.

Osteoporotic hip fractures (OHF) are not limited to elderly; however, studies in non-elderly are scarce. Thus, the aim of this study was to evaluate co-morbidities in non-elderly patients with OHF in a Community Teaching Hospital. All hospitalizations due to OHF during a 3-year period in a Community Teaching Hospital were retrospectively evaluated for co-morbidities, and patients 18–64 years old were compared with those ≥65 years old. Of all hospitalizations, 232 (0.73%) were due to hip fractures, and 120/232 (51.7%) patients had OHF. The comparison of the 13 (10.8%) OHF patients

BackgroundDespite the WHO recommendation that the 2010–2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population.Methods1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçet's disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögren's syndrome, Takayasu's arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener's) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated.ResultsAfter immunisation, seroprotection rates (68.5% vs 82.9% pConclusionsThe novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety.(ClinicalTrials.gov #NCT01151644)