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IntroductionWomen with systemic lupus erythematosus (SLE) have increased prevalence of precancer cervical squamous intraepithelial lesions (SIL). This study aimed to compare human papillomavirus (HPV) seroprevalence, cervical HPV-DNA detection and HPV-related cervical lesions between SLE and immunocompetent women.MethodsIn this cross-sectional study, women aged 18–45 years with SLE receiving immunosuppressive or disease-modifying antirheumatic drugs were compared with immunocompetent women, selected from the same hospital in Sao Paulo, Brazil. Eligible participants had no self-reported history of genital warts or any other HPV-related cervical, vaginal or vulvar lesions, nor received prior HPV vaccination. Cervical samples were tested for HPV-DNA using PapilloCheck and for SIL lesions by liquid-based cytology. A multiplex pseudovirion-based serology assay (PsV-Luminex) measured serum antibodies against eight of the HPV types targeted by non-valent (9vHPV) HPV vaccine.ResultsA total of 122 women with SLE and 132 immunocompetent women (mean age 34.3 and 32.5 years, respectively) were enrolled. Compared with immunocompetent women, SLE participants had higher prevalence of HPV-related cervical lesions (low-grade and high-grade SIL combined, 11.3% vs 2.4%, p=0.009), higher prevalence of at least one cervical HPV type (38.8% vs 20.2%, p=0.003), non-significantly higher prevalence of cervical high-risk HPV types (23.5% vs 14.9% p=0.286) and higher HPV seroprevalence to eight HPV types included in the 9vHPV vaccine (80.4% vs 59.7%, p=0.001).ConclusionOur findings underscore the importance of tailored cervical cancer screening and HPV vaccination of SLE women at young age.

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. In a large prospective phase 4 trial, vaccination with CoronaVac, an inactivated SARS-CoV-2 vaccine, elicited significantly lower virus-specific IgG antibodies and neutralizing antibodies in patients with autoimmune rheumatic diseases than in age- and sex-matched healthy control trial participants.

IntroductionThe American Academy of Ophthalmology (2016-AAO) recommended hydroxychloroquine (HCQ) dose not to exceed 5 mg/kg/day (real body weight). Recently, it was reported that prescribed 2016-AAO dose provided adequate HCQ levels for most lupus nephritis (LN) patients, with low flare risk. However, the minimum HCQ dose required to keep adequate levels is unknown.ObjectivesTo evaluate if a further reduction in 2016-AAO dose (2–3 mg/kg/day) would sustain 12-month HCQ levels in LN patients with stable inactive disease.MethodsSeventy-three stable LN patients under prescribed full HCQ 2016-AAO dose for ≥6 months and adequate baseline HCQ levels (≥613.5 ng/mL) were divided in two groups: reduced 2016-AAO dose (2–3 mg/kg/day), n = 32, and full 2016-AAO dose (5 mg/kg/day), n = 41. All patients were assessed at baseline, 3, 6, and 12 months. HCQ levels were measured by liquid chromatography-tandem mass spectrometry. Flare was defined as augment ≥ 3 in SLE Disease Activity Index-2000 and/or change in treatment. Rigorous clinical/laboratorial surveillance was performed.ResultsProspective evaluation revealed for reduced 2016-AAO dose group a decrease of HCQ levels from baseline to 3 months (1,404.9 ± 492.0 vs. 731.6 ± 385.0 ng/mL, p < 0.01), and sustained levels at 6 months (p = 0.273) and 12 months (p = 0.091) compared to 3 months. For the full 2016-AAO dose group, a decrease occurred only from baseline to 12 months (1343.5 ± 521.5 vs. 991.6 ± 576.3 ng/mL, p < 0.001). Frequencies of patients with inadequate levels at 6 months was higher in reduced 2016-AAO group than full 2016-AAO dose (59% vs. 24%, p = 0.005), as well as at 12 months (66% vs. 32%, p = 0.002). Six-month and 12-month flare frequencies were comparable for both groups (p > 0.05).ConclusionsPrescribed HCQ low-dose regimen (2–3 mg/kg/day) does not sustain, for most patients, 6- and 12-month adequate HCQ levels. Full 2016-AAO dose maintained HCQ levels way above this limit.Trail registrationClinicalTrials.gov: NCT03122431, registered on April 20, 2017Key Points• Reduced American Academy of Ophthalmology (2016-AAO) hydroxychloroquine (HCQ) dose (2–3 mg/kg/day, real body weight) is unable to sustain HCQ blood levels within the safe cut-off defined for flare risk.• Full 2016-AAO dose (5 mg/kg/day) maintains a safe pattern of HCQ levels up to 12 months.

The objective of this study is to assess the role of the 2019-European League Against Rheumatism/American College of Rheumatology (2019-EULAR/ACR) classification criteria at diagnosis and its domains in predicting long-term damage in systemic lupus erythematosus(SLE). We performed a retrospective analysis using an electronic chart database utilized in routine clinical care of SLE patients and established in 2000 in a tertiary hospital. Two hundred and nine consecutive SLE patients with disease onset ≥18 years old and long disease duration were included. Cumulative damage at the last visit was scored using the SLICC/ACR-Damage Index (SDI). The median age at SLE diagnosis was 28 years (18–63), disease duration was 14 years (8–25), and 88% were females. Damage (SDI≥1) was observed in 116/209 (55%). Patients with (SDI≥1, n =116) and without damage (SDI=0, n =93) had similar median disease duration [14 (8–25) vs. 12 (8–25) years, p =0.090] and age at diagnosis [23 (18–55) vs. 23 (18–56) years, p =0.998]. No correlation was observed between total 2019-EULAR/ACR score at diagnosis and SDI at last visit ( r =0.007, p =0.913). Presence of renal domain at diagnosis was associated with renal damage at last visit (OR=3.6, 95%CI 1.2–10.4, p =0.017) and antiphospholipid antibodies domain predicted neuropsychiatric damage (OR=3.0, 95%CI 1.2–7.6, p =0.015). A ROC analysis identified that a cut-off >24 in 2019-EULAR/ACR score could predict a trend for renal damage ( p =0.077) with a lower renal survival (Kaplan-Meier curve) for patients above this limit ( p =0.029). A multivariate logistic regression analysis revealed that 2019-EULAR/ACR score >24 at diagnosis (OR 4.583, 95%CI 1.052–19.962, p =0.043) was independently associated with renal damage. Specific domains in the 2019-EULAR/ACR criteria at diagnosis were associated with long-term organ-specific damage, particularly renal and neuropsychiatric harm. A 2019-EULAR/ACR score >24 predicted worse renal survival. Key Points • Presence of renal domain of the 2019-EULAR/ACR classification criteria at diagnosis was associated with long-term renal damage. • Presence of antiphospholipid antibodies domain at diagnosis was associated with long-term neuropsychiatric damage. • A 2019-EULAR/ACR overall score >24 at diagnosis was independently associated with renal damage and predicted worse renal long-term survival.

ObjectiveAfrican-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).MethodsSera 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.ResultsAfrican-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).ConclusionAfrican-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 Despite 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. Methods 1668 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. Results After immunisation, seroprotection rates (68.5% vs 82.9% p<0.0001), seroconversion rates (63.4% vs 76.9%, p<0.001) and the factor increase in GMT (8.9 vs 13.2 p<0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p<0.0001), RA (p<0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p<0.0001), RA (p<0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p<0.0001), RA (p<0.0001) and PsA (p<0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The 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)

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 <65 years old (47.3 ± 9.7 years) with 107 (89.2%) ≥65 years old (80.4 ± 7.7 years) revealed a male predominance (61.5 vs. 27.1%, P  = 0.022) and a distinct ethnic distribution with a lower proportion of Caucasians in the former (61.5 vs. 86.9%, P  = 0.033). Moreover, non-elderly OHF patients had higher frequencies of insulin-dependent DM (38.5 vs. 3.7%, P  = 0.001) and alcoholism (38.5 vs. 4.7%, P  = 0.001) than aged patients. In contrast, rates of age-related co-morbidities such as stroke (7.7 vs. 18.7%, P  = 0.461), heart failure (23.1 vs. 14.0%, P  = 0.411), and dementia (7.7 vs. 15.9%, P  = 0.689) were comparable in both groups. Logistic regression analysis demonstrated that insulin-dependent DM (OR = 25.4, 95% CI = 4.7–136.8, P  < 0.001) and alcoholism (OR = 20.3, 95% CI = 3.9–103.3, P  < 0.001) remained as independent risk factors for OHF in non-elderly patients. Osteoporosis is an important cause of HF in Community Hospital. Non-elderly patients with OHF have a peculiar demographic profile and associated co-morbidities. These findings reinforce the need of early osteoporosis diagnosis and rigorous fracture prevention in patients with DM and alcoholism.

This study aimed to investigate whether a single bout of exercise prior to the homologous booster dose of a SARS-CoV-2 inactivated vaccine (Sinovac-CoronaVac) could enhance immunogenicity in patients with dysfunctional immune system. This was a randomized controlled trial (1:1) within a single-arm, phase 4 vaccination trial, conducted in São Paulo, Brazil. Patients with spondyloarthritis assigned to the intervention group performed an exercise bout comprising three unilateral strength exercises involving eccentric and concentric contractions. After exercising, patients remained at rest for 1 h prior to vaccination, which was applied to the exercised arm. The control group remained at rest before vaccination. Immunogenicity was assessed before (Pre) and one month after (Post) the booster dose using seropositivity rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), frequency of NAb positivity, and NAb activity. Before the booster dose, 16 patients from the exercise group and 16 patients from the control group exhibited seropositivity for IgG (59% vs. 57.1%), one month after the booster dose, seropositivity occurred in 96% vs. 100% of the cases (p = 0.84, group by time interaction). Only 10 patients from the exercise group and 12 patients from the control group showed positive NAb serology at Pre (37% vs. 42.8%). One month following the booster, NAb positivity was 96% vs. 93% (p = 0.41, group-by-time interaction). GMT was comparable between groups at Pre (p > 0.05). At Post, GMT increased similarly in both groups (exercise: 56.9%; control: 57.9%), with no group-by-time interaction (p = 0.82; estimated mean difference between groups at Post [EMD]: -40.4 UA/mL, 95%CI: -327, 246 UA/mL). Likewise, NAb activity was similar between groups at Pre and increased similarly in both of them as a result of the booster (47.5% vs. 39.9%), with no group-by-time interaction (p = 0.99; EMD: -6.19%, 95%CI: -17; 4.6%). In conclusion, a single bout of exercise did not enhance immunogenicity to a homologous booster dose of an inactivated SARS-CoV-2 vaccine among patients with spondyloarthritis. Studies assessing exercise as an adjuvant to first or second doses remain necessary.

This chapter discusses the endometriosis (EM) and autoimmunity. EM is a disorder of the female reproductive system characterized by the presence of endometrial tissue outside the uterine cavity, most commonly on fallopian tubes, ovaries, pelvic peritoneum, rectovaginal septum, bladder, and rectum. EM is a major cause of pelvic pain and infertility in women during reproductive age. The diagnosis should be confirmed by a surgical procedure, generally laparoscopy, to identify, excise, and histologically evaluate the pelvic lesions. There are several studies in the literature suggesting an intriguing association of EM with autoimmune diseases, particularly SLE. EM does not appear to be associated with autoimmune rheumatological diseases. These patients do, however, have a high frequency of musculoskeletal symptoms and fibromyalgia. Clustering of auto-antibodies associated with autoimmune diseases occurs in EM patient sera, suggesting that a common mechanism may underlie both EM and rheumatological autoimmune diseases. However, lupus-specific auto antibodies such as anti-dsDNA and anti-Sm are not observed in EM.

Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) may coexist, and they are chronic complex disorders, with an autoimmune background, multifactorial etiology, multiple circulating autoantibodies, and variable prognosis. The prominent feature of SS is the impairment of the lacrimal and salivary glands leading to sicca symptoms. This disease may be classified as primary Sjögren's syndrome (pSS), or secondary Sjögren's syndrome (sSS) since it is often associated to other autoimmune disorders, principally SLE, rheumatoid arthritis, and systemic sclerosis. Systematic reviews and meta-analyses show an sSS prevalence in SLE patients of about 14%-17.8%. Herein, we updated important aspects of the clinical association between SLE and sSS through a narrative review of the PubMed database in the last 5 years (from July 2013 to October 2018) with the terms \"Sjogren syndrome and systemic lupus erythematosus\". The following aspects are addressed: the classification criteria for sSS; differences and similarities between SLE and pSS regarding demographic, clinical, and serological characteristics (including new autoantibodies), as well as comorbidities; the etiopathogenic links between SLE and pSS (including genetic and environmental factors, B-cell activation, and autoantibodies); the predictive factors for sSS onset in SLE patients; the ocular and oral involvements due to sSS in SLE; and the main distinctive demographic, clinical, and serological features of SLE with and without associated SS.