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Objective: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN)., Methods: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion., Results: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy., Conclusion: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil., (© 2024. The Author(s).)

Background: The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C-rs1042522; p53 PIN3-rs17878362; p21 31 C > A-rs1801270; p21 70 C > T-rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population., Methods: Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis., Results: Protective effect was observed for the genotype combinations p53 PIN3 A1/A1-p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively)., Conclusions: Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients., (© 2023. Sociedade Brasileira de Reumatologia.)

Objective: The aim of this study was to analyze the occurrence and risk factors associated with infections during pregnancy in patients with systemic lupus erythematosus., Methods: This is a retrospective cohort study using the data of pregnant women who were followed up between 2011 and 2018 at a university hospital., Results: The data of 221 pregnant women with systemic lupus erythematosus were analyzed. The incidence of infections was 22.6% (50/221), with the urinary tract being the most frequent site of infection (32/221, 14.5%) followed by the respiratory tract (15/221, 6.8%). The bivariate analysis showed that active disease, hematological systemic lupus erythematosus, reduced complement, and use of prednisone ≥5 and ≥10 mg increased the chance of infection during early pregnancy (p=0.05, p=0.04, p=0.003, p=0.008, and p=0.02, respectively), while disease activity and anti-DNA positivity increased it at the end of pregnancy (p=0.03 and p=0.04, respectively). Prednisone at a dose ≥5 mg increased the chance of infection in the beginning (p=0.01) and at the end of pregnancy (p=0.008). Multivariate analysis showed that increasing the dose of prednisone from 5 to 10 mg tripled the chance of developing infections in pregnant women with lupus (p=0.02)., Conclusion: The study showed an increased chance of infections in pregnant women with systemic lupus erythematosus and it was associated with the use of prednisone.

Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil., Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19., Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98)., Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6)., (© 2021. The Author(s).)

Objective: To evaluate mean serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and soluble Flt-1 (sFlt-1) in pregnant patients with systemic lupus erythematosus (SLE) with inactive disease, active lupus nephritis, and preeclampsia for differential diagnosis between these conditions., Methods: Pregnant women with SLE, with singleton pregnancies and no other autoimmune diseases, were classified according to disease activity (inactive SLE and active lupus nephritis) and the presence of preeclampsia. Serum samples were collected within 3 weeks of delivery and frozen for subsequent blinded analysis through the enzyme-linked immunosorbent assay method., Results: A total of 71 women were included, with 41 classified as having inactive SLE (group 1; Systemic Lupus Erythematosus Pregnancy Disease Activity Index [SLEPDAI] score <4), 15 with a diagnosis of active lupus nephritis (group 2, SLEPDAI score ≥4, including renal criteria), and 15 with a diagnosis of preeclampsia (group 3). Patients in group 3 had higher mean levels of sFlt-1 and lower mean levels of PlGF compared to groups 1 and 2, both findings with statistical significance. The sFlt-1:PlGF ratio was also significantly higher in patients with preeclampsia, while mean VEGF levels were higher in pregnant woman with active lupus nephritis compared to patients with preeclampsia or inactive SLE., Conclusion: Evaluation of serum VEGF, PlGF, and sFlt-1 levels can differentiate between preeclampsia, inactive SLE, and active lupus nephritis during pregnancy., (© 2020, American College of Rheumatology.)

Background: In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving ≥80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations., Conclusion: This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting vaccination practices. We recommended a shared decision-making approach on taking or not the YFV.

Introduction: In contrast to organ transplantation, few studies correlate the monitoring of pp65 antigenemia with a diagnosis of cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE)., Objective: To highlight the importance of CMV outside transplantation, we monitored pp65 antigenemia in a series of SLE patients., Methods: From March 2015 to March 2016, SLE patients presenting kidney involvement, fever, and an unclear infection at hospital admission were monitored through pp65 antigenemia. The pp65 antigenemia assay, revealed by immunofluorescence, was correlated with clinical and laboratory findings., Results: We included 19 patients with a suspected unclear infection. A positivity for pp65 antigenemia was found in seven patients (36.8%). The mean age was 33.5 ± 11.2 years, 16 (84%) were females, and 16 (84%) were black. Lymphopenia, anemia, and higher scores of SLEDAI were significantly more common in pp65-positive patients. Five patients received antiviral therapy with ganciclovir. Although receiving specific CMV treatment, one patient died because of suspected CMV disease., Conclusions: Pp65 antigenemia might be relevant in SLE patients, and studies with a greater number of patients are needed in order to establish sensitivity and specificity of pp65 antigenemia in different clinical contexts of SLE patients.

Objective: To investigate potential associations of four substitutions in NAT2 gene and of acetylator phenotype of NAT2 with systemic lupus erythematosus (SLE) and clinical phenotypes., Methods: Molecular analysis of 481C>T, 590G>A, 857G>A, and 191G>A substitutions in the NAT2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, from DNA extracted from peripheral blood samples obtained from patients with SLE (n=91) and controls (n=97)., Results and Conclusions: The 857GA genotype was more prevalent among nonwhite SLE patients (OR=4.01, 95% CI=1.18-13.59). The 481T allele showed a positive association with hematological disorders that involve autoimmune mechanisms, specifically autoimmune hemolytic anemia or autoimmune thrombocytopenia (OR=1.97; 95% CI=1.01-3.81)., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

Background: Treatment adherence is a primary determinant of the success and effectiveness of healthcare. Lack of adherence can lead to treatment failure and death. Although studies have shown that pharmaceutical intervention can improve drug treatment for patients with chronic diseases, studies on pharmaceutical care are not only inconsistent, they are scarce and limited to developed countries, include few patients, and are not studied in randomized clinical trials. Systemic lupus erythematosus is an autoimmune disease with high hospitalization and case-fatality rates. The adherence rate is low (31.7 %) in this group of patients in Brazil, and drug treatment for the disease is complex. Our objective is to evaluate the effectiveness of pharmaceutical care in drug treatment adherence in patients with systemic lupus erythematosus treated at a rheumatology outpatient clinic in Rio de Janeiro, Brazil., Methods: A randomized clinical trial (pragmatic trial) will be conducted. Adult participants (women) from a public hospital in Rio de Janeiro with a diagnosis of systemic lupus erythematosus will be followed for 12 months. A total of 120 patients will be randomized to two groups: intervention (Dader method for pharmaceutical care) and control (health/dietary counseling and risk reduction). The primary outcome will be drug treatment adherence evaluated by the eight-item Morisky Medication Adherence Scale. Secondary outcomes will be clinical improvement and quality of life., Discussion: Patients with systemic lupus erythematosus present with low treatment adherence, thus justifying the mobilization of human resources to optimize their clinical management. Despite the proven effectiveness of pharmaceutical care for various diseases, there are still no studies evaluating its effectiveness in systemic lupus erythematosus. Our hypothesis is that the intervention will also be effective in this patient group., Trial Registration: ClinicalTrials.gov identifier: NCT02330250 .

Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease that occurs predominantly in women of fertile age. The association of SLE and pregnancy, mainly with active disease and especially with nephritis, has poorer pregnancy outcomes, with increased frequency of preeclampsia, fetal loss, prematurity, growth restriction, and newborns small for gestational age. Therefore, SLE pregnancies are considered high risk condition, should be monitored frequently during pregnancy and delivery should occur in a controlled setting. Pregnancy induces dramatic immune and neuroendocrine changes in the maternal body in order to protect the fetus from immunologic attack and these modifications can be affected by SLE. The risk of flares depends on the level of maternal disease activity in the 6-12 months before conception and is higher in women with repeated flares before conception, in those who discontinue useful medications and in women with active glomerulonephritis at conception. It is a challenge to differentiate lupus nephritis from preeclampsia and, in this context, the angiogenic and antiangiogenic cytokines are promising. Prenatal care of pregnant patients with SLE requires close collaboration between rheumatologist and obstetrician. Planning pregnancy is essential to increase the probability of successful pregnancies.

Objective: To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil., Method: Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology., Results and Conclusions: 1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. 2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. 3) Risks and benefits of treatment should be shared with the patient and his/her family. 4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. 5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). 6) ACE inhibitors and/or ARBs are recommended as antiproteinuric agents for all patients (unless contraindicated). 7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including steroids and an immunosuppressive agent, even though histological confirmation is not possible. 8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient achieve and maintain a sustained and complete remission. 9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when a new renal biopsy should be considered to assist in identifying the cause of refractoriness and in the therapeutic decision., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

Here, we describe an atypical case of systemic sclerosis in its diffuse cutaneous form with acute and rapid progression of the cutaneous condition, without any systemic manifestations and the infrequent formation of bullae, showing the importance of diagnosis and early treatment in such cases. This case also shows that special measures should be taken for bullous cutaneous lesions and ulcerations resulting from serious sclerosis, which are entry points and increase morbidity and risk of death. Other prognostic factors include age, ESR and renal and pulmonary involvement. Capillaroscopies can be useful predictors of greater severity of systemic scleroderma, revealing a greater link with systemic, rather than cutaneous, involvement.

Background: Takayasu arteritis (TA) is a rare chronic granulomatous inflammatory disease of the aorta and/or its major branches and more frequently affects female patients before menopause. Since persistent inflammation may lead to arterial ischemia, hypertension is an important complication of TA., Objectives: To evaluate gestational results and complications in patients with TA., Methods: We conducted a retrospective analysis of the medical records of patients with TA admitted to the high risk pregnancy clinic for women with systemic autoimmune diseases at Hospital Universitário Pedro Ernesto., Results: From 1998 to 2011 we followed 11 pregnancies in 9 patients with TA; the patients' age ranged from 17 to 42 years and disease duration from 2 to 28 years. In 7 of the 11 pregnancies, uncontrolled blood pressure occurred before labor and preeclampsia was diagnosed in one. Two deliveries were preterm, one newborn was treated for sepsis, and four (36%) had intrauterine growth restriction (IUGR)., Conclusions: Close monitoring improves the perinatal outcomes in patients with TA who are more prone to develop hypertension, preeclampsia and IUGR. Disease activity was not observed in our group of patients during pregnancy. Coordinated care between the obstetric, rheumatologic and cardiologic teams is the ideal setting to follow pregnant women with TA.

Background: Systemic lupus erythematosus (SLE) often requires administration of cyclophosphamide (CYC), especially for severe glomerulonephritis. As this disease usually affects young women in reproductive age, pregnancy, though not recommended may occur. The teratogenic effects of this drug make pregnancy prognosis and fetal survival indeterminate., Methods: We reviewed retrospectively the medical records of five patients with SLE who received inadvertently CYC during pregnancy and analyzed fetal outcome., Results: All patients were exposed at the first trimester. Two patients suffered miscarriages, two went to full term and one presented premature labor., Conclusion: In spite of potential successful pregnancies after CYC exposure, this drug has teratogenic effects and prescription must be avoided during the pregnancy period. At the same time, the occurrence of these reported unplanned pregnancies strengthen the need of improving patients' education on pregnancy risks during immunosuppressive treatment.

A strong aging tendency is currently being observed in the world population, leading to an increase n the prevalence of such diseases as osteoporosis and fractures. This study aimed to determine the prevalence of fracture risk, estimated by quantitative ultrasound of the calcaneus in a population of postmenopausal women residing in the Ilha de Paquetá neighborhood of Rio de Janeiro, Brazil. We conducted anthropometric measurements and quantitative ultrasound of the calcaneus using Sonost 2000 in 385 postmenopausal women. Some 59.22% of the sample showed a T-score < -1, while 16.88% had T-score < -2.5. The test parameters varied with increasing age, with a statistically significant difference (p < 0.05) between fracture risk groups according to age, time since menopause, weight, BMI, and body fat. There was a correlation between sound velocity and BMI (r = 0.155; p = 0.002). We concluded that some 60% of the female study population showed some degree of fracture risk. The women at highest risk (T-score < -2.5) were older, with more time since menopause, and had higher weight and BMI as compared to the other groups.