Abstract Objective To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. Materials and methods The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. Results Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. Conclusion The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases. MEDLINE LILACS Library databases records investigators analysis infections teratogenicity Longterm Long term longterm long 3 g discontinuation 1 41 41% bias i.e., ie i e (i.e. g, , g) intake anticoagulants disease cases 4 i.e. (i.e i.e

Abstract 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. evidencebased evidence LN. . (LN) 2 guideline performed remission doubling endstage end stage disease relapse infections mortality. mortality mortality) Assessment GRADE (GRADE 82 ≥82 favor conditional intervention diagnosis, (diagnosis opinion involvement but procedure parameters developed TRR (TRR ±10% 10 (±10 24h 24 25 months 50 08 0 8 0. g24 g g/2 1 period ±V, V ±V , (±V) MMF, (MMF) cyclophosphamide TAC, (TAC) therapy AZA (AZA adherence dosage biopsyrebiopsy rebiopsy biopsy/rebiopsy Brazil (LN ≥8 ±10 (±1 5 g2 g/ (±V (MMF (TAC ≥ ±1 (± ± (

Abstract Objective: To provide guidelines on the coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated rheumatic diseases (IMRD) to rheumatologists considering specific scenarios of the daily practice based on the shared-making decision (SMD) process. Methods: A task force was constituted by 24 rheumatologists (panel members), with clinical and research expertise in immunizations and infectious diseases in immunocompromised patients, endorsed by the Brazilian Society of Rheumatology (BSR), to develop guidelines for COVID-19 vaccination in patients with IMRD. A consensus was built through the Delphi method and involved four rounds of anonymous voting, where five options were used to determine the level of agreement (LOA), based on the Likert Scale: (1) strongly disagree; (2) disagree, (3) neither agree nor disagree (neutral); (4) agree; and (5) strongly agree. Nineteen questions were addressed and discussed via teleconference to formulate the answers. In order to identify the relevant data on COVID-19 vaccines, a search with standardized descriptors and synonyms was performed on September 10th, 2021, of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and LILACS to identify studies of interest. We used the Newcastle–Ottawa Scale to assess the quality of nonrandomized studies. Results: All the nineteen questions-answers (Q&A) were approved by the BSR Task Force with more than 80% of panelists voting options 4—agree—and 5—strongly agree—, and a consensus was reached. These Guidelines were focused in SMD on the most appropriate timing for IMRD patients to get vaccinated to reach the adequate covid-19 vaccination response. Conclusion: These guidelines were developed by a BSR Task Force with a high LOA among panelists, based on the literature review of published studies and expert opinion for COVID-19 vaccination in IMRD patients. Noteworthy, in the pandemic period, up to the time of the review and the consensus process for this document, high-quality evidence was scarce. Thus, it is not a substitute for clinical judgment.

RESUMO Paciente do sexo feminino, 29 anos de idade, com diagnóstico de lúpus eritematoso sistêmico em uso atual de prednisona e azatioprina, se apresenta com abaulamentos em antebraços, região lombar e coxa esquerda há 15 dias. A ultrassonografia e a ressonância magnética evidenciaram presença de coleções nesses locais cuja punção do material revelou presença de bacilos álcool ácido resistentes e a hemocultura, em meio específico, foi positiva para Mycobacterium tuberculosis. O teste molecular e imunocromatográfico também foram positivos para M. tuberculosis, com diagnóstico final de Piomiosite Tuberculosa.

ABSTRACT Female patient, 29 years old, with systemic lupus erythematosus in current use of prednisone and azathioprine, presents with bulging in the forearms, lumbar region and left thigh for 15 days. Ultrasonography and magnetic resonance imaging showed the presence of serous collections in these locations. The material was punctured and the samples were sent to the laboratory. The microbiological examination revealed the presence of acid-resistant bacilli and blood culture in a specific medium was positive for Mycobacterium tuberculosis. Molecular and immunochromatographic tests were positive for M. tuberculosis, and the diagnosis of Tuberculous Piomyositis was closed.

Abstract Background: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID 19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID 19 hospitalizations in patients with RA. Methods: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID 19 were compared to 220 patients who tested negative for COVID 19 (control group). All patient data were collected from the Research Electronic Data Capture database. Results: The participants were predominantly female (90.6%) with a mean age of 53 ±12 years. Of the patients with COVID 19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR =4.61, 95% CI 1.06–20.02. P < 0.001) and current use of glucocorticoids (OR =20.66, 95% CI 3.09–138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR =0.26; 95% CI 0.10–0.67, P < 0.005). Conclusion: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID 19 in patients with RA. Trial registration: Brazilian Registry of Clinical Trials RBR 33YTQC.

Abstract Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.

Abstract Objective: To determine the incidence of positive CMV antigenemia (CMV-Ag) in patients with autoimmune rheumatic diseases (AIRD) and to describe the outcomes of these patients. Methods: From January 2011 to December 2014, a total of 443 patients with AIRD were enrolled in this retrospective analysis. Demographic, clinical and laboratory data, current clinical manifestations, organs affected by CMV infection, therapeutic management and outcomes were evaluated. The CMV-Ag was considered positive when one cell was detected at least. Results: CMV-Ag was requested in 70 (15.8%) patients with suspicious CMV infection and was positive in 24 (34.3%). The incidence rate of positive CMV-Ag was 4.97% (95% CI 3.1-7.4%). Systemic lupus erythematosus (SLE) (59%), followed by ANCA-related vasculitis (18.2%) and rheumatoid arthritis (9%) were the diseases more associated with positive CMV-Ag. At the time of CMV infection, SLE patients had moderate to severe disease activity, with high frequency of positive anti-dsDNA antibody (69.2%) and complement consumption (61.5%), as well as high doses of corticosteroids and use of immunosuppressants. The main CMV sites involved were lung (45.5%), bone marrow (40. 9%) and gut (27.3%). Mortality rate was 45.5%, especially in those with higher doses of daily oral corticosteroids (107 ±55.4 mg vs. 71.7 ±46.3 mg; p = 0.07) and lower number of lymphocytes (309 ± 368.2/mm3 vs. 821 ± 692.9/ mm3; p = 0.06). Conclusions: Our data showed high incidence of CMV-Ag in AIRD patients, particularly those with SLE and greater disease severity. In addition, it was observed high mortality in these patients, highlighting the CMV infection should be included in differential diagnosis.

Abstract Background: It has long been established that obesity plays a positive role against osteoporosis (OP) and low-impact fractures (Fx). However, more recent data has shown higher fracture risk in obese individuals. The aim of this study was to investigate the association between BMI, particularly obesity, OP and low-impact Fx in Brazilian women, as well as to evaluate the SAPORI (Sao Paulo Osteoporosis Risk Index) tool performance to identify low BMD according BMI category. Methods: A total of 6182 women aged over 40 years were included in this cross-sectional analysis using data from two large Brazilian studies. All participants performed hip and spine bone mineral density (BMD) measurements and answered a detailed questionnaire about the presence of clinical risk factors (CRFs) related to low BMD and risk fractures. The World Health Organization (WHO) criteria were used to define obesity. Results: Age-adjusted osteoporosis prevalence was 20.8, 33.6, 47 and 67.1% in obese, overweight, normal and underweight category, respectively. Obesity was present in 29,6% (1.830 women) in the study population and the likelihood of osteoporosis and low-impact Fx compared to a normal BMI in this subgroup was of 0.24 (95% CI 0.20– 0.28; p < 0.001) and of 1.68 (95% CI 1.35–2.11; p < 0.001), respectively. However, the hip Fx likelihood was lower in obese compared with non-obese women (OR = 0.44; 95% CI 0.20–0.97). Using an originally validated cut-off, the SAPORI tool sensitivity was significantly hampered in overweight and obese women although the accuracy had remained suitable because of increasing in specificity. Conclusions: The osteoporosis prevalence reduced as BMI increased and obesity was associated with low-impact Fx, regardless of the BMD measurements. Moreover, the SAPORI performance was impaired in obese women.

OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab.

Os autores relatam caso de tuberculose cutânea disseminada com escrofuloderma associado à tuberculose de arco costal. Paciente de 46 anos, do sexo feminino, há um ano com nódulos de um a 6cm em região cervical, dorso, axilas e regiões glúteas, que culminavam com fistulização e eliminação de secreção purulenta, associados a febre vespertina diária, sudorese noturna e emagrecimento de 10kg nos últimos três meses. A radiografia de tórax mostrou lesão lítica na terceira costela esquerda. A cultura de secreção do nódulo foi positiva para Mycobacterium tuberculosis. O tratamento para tuberculose resultou em melhora clínica e resolução das lesões cutâneas da paciente.

The authors describe a case of disseminated cutaneous tuberculosis with scrofuloderma associated to tuberculosis in the costal arch. A 46-year-old, woman, was hospitalized with nodules measuring 1 to 6 cm in the cervical region, back, armpit and buttocks, which developed purulent discharge with elimination of caseous secretion, associated to episodes of daily evening fever, night sweats and weight loss of 10Kg over the previous three months. Thorax radiography showed an osteolytic lesion in the third left rib. Culture of the nodule secretion was positive for Mycobacterium tuberculosis. Treatment for tuberculosis resulted in pronounced clinical improvement and resolution of the patient's cutaneous lesions.