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 Introduction Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature. Objective To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE. Methods 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/ INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated. Results JSLE patients and controls were comparable in current age [14.5 (10.1–18.3) vs. 14 (9–18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0–139.4) vs. 109.6 (95% CI 68.2–176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9–198.3) vs. 208.1 (150.5–287.8), p = 0.143] and factor increase in GMT [1.6 (1.2–2.1) vs. 1.9 (1.4–2.5), p = 0.574]. SLEDAI-2K scores [2 (0–17) vs. 2 (0–17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 ( p = 0.713), as well as between patients with and without current use of prednisone ( p = 0.420), azathioprine ( p = 1.0), mycophenolate mofetil ( p = 0.185), and methotrexate ( p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups ( p > 0.05). Conclusion This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www.clinicaltrials.gov , NCT03540823). H3N2 HN H N (H3N2 5 H1N1 (JSLE literature shortterm short term ASingapore Singapore (HC INFIMH160019/2016H3N2like INFIMH1600192016H3N2like INFIMHHNlike INFIMH 16 0019/2016 like 0019 2016 SP, (SP) SC, (SC) GMT, (GMT) FIGMT FI (FI-GMT postvaccination. postvaccination post vaccination. vaccination post-vaccination activity (AE evaluated 14.5 145 [14. 10.1–18.3 101183 10 1 18 3 (10.1–18.3 vs 9–18.4 9184 (9–18.4 0.448 0448 0 448 21 87.5% 875 87 (87.5% 65.5%, 655 65.5% 65 (65.5%) 0.108. 0108 0.108 . 108 0.108] 22 91.7% 917 91 7 (91.7% 86.2%, 862 86.2% 86 (86.2%) 0.678 0678 678 102.3 1023 102 [102. 95% 95 (95 75.0–139.4 7501394 75 139 1096 109 6 109. 68.2–176.2, 6821762 68.2–176.2 68 176 68.2–176.2) 0.231. 0231 0.231 231 0.231] D30 D 100% 100 (100% 96.6%, 966 96.6% 96 (96.6%) 1.000, 1000 1.000 000 1.000)] [ 16.7% 167 (16.7% 31.0%, 310 31.0% 31 (31.0%) 0.338, 0338 0.338 338 0.338) 162.3 1623 162 [162. 132.9–198.3 13291983 132 198 (132.9–198.3 2081 208 208. 150.5–287.8, 15052878 150.5–287.8 150 287 8 (150.5–287.8) 0.143 0143 143 1.6 [1. 1.2–2.1 1221 (1.2–2.1 1. 1.4–2.5, 1425 1.4–2.5 (1.4–2.5) 0.574. 0574 0.574 574 0.574] SLEDAI2K SLEDAIK 2K K 0–17 017 17 (0–17 0–17, 0.765 0765 765 0.713, 0713 0.713 713 0.713) 0.420, 0420 0.420 420 0.420) 1.0, 1.0 1.0) 0.185, 0185 0.185 185 0.185) 0.095. 0095 0.095 095 0.095) 58.3% 583 58 (58.3 44 44.8% 0.958. 0958 0.958 958 0.958) 0.05. 005 0.05 05 0.05) H3N2influenza HNinfluenza vaccineinduced induced wwwclinicaltrialsgov www clinicaltrials gov NCT03540823. NCT03540823 NCT NCT03540823) H3N (H3N H1N INFIMH160019 2016H3N2like 00192016 0019/201 001 201 (SP (SC (GMT 14. [14 10.1–18. 10118 (10.1–18. 9–18. 918 (9–18. 0.44 044 87.5 (87.5 65.5 (65.5% 010 0.10 91.7 (91.7 86.2 (86.2% 0.67 067 67 102. [102 (9 75.0–139. 750139 13 682176 68.2–176. 023 0.23 23 D3 (100 96.6 (96.6% 1.00 00 1.000) 16.7 (16.7 31.0 (31.0% 033 0.33 33 162. [162 132.9–198. 1329198 (132.9–198. 20 1505287 150.5–287. 15 (150.5–287.8 0.14 014 [1 1.2–2. 122 (1.2–2. 142 1.4–2. (1.4–2.5 057 0.57 57 0–1 01 (0–1 0.76 076 76 071 0.71 71 042 0.42 42 018 0.18 009 0.09 09 58.3 (58. 44.8 0.95 0.0 NCT0354082 INFIMH16001 HNlike 0019201 0019/20 10.1–18 1011 (10.1–18 9–18 (9–18 0.4 04 87. (87. 65. (65.5 0.1 91. (91. 86. (86.2 0.6 06 [10 75.0–139 75013 68217 68.2–176 02 0.2 (10 96. (96.6 16. (16. 31. (31.0 03 0.3 [16 132.9–198 132919 (132.9–198 150528 150.5–287 (150.5–287. 1.2–2 12 (1.2–2 1.4–2 (1.4–2. 0.5 0– (0– 0.7 07 58. (58 44. 0.9 0. NCT035408 INFIMH1600 001920 0019/2 10.1–1 101 (10.1–1 9–1 (9–1 (87 (65. (91 (86. 75.0–13 7501 6821 68.2–17 (1 (96. (16 (31. 132.9–19 13291 (132.9–19 15052 150.5–28 (150.5–287 1.2– (1.2– 1.4– (1.4–2 (0 (5 NCT03540 INFIMH160 00192 0019/ 10.1– (10.1– 9– (9– (8 (65 (86 75.0–1 750 682 68.2–1 (96 (31 132.9–1 1329 (132.9–1 1505 150.5–2 (150.5–28 1.2 (1.2 1.4 (1.4– NCT0354 INFIMH16 10.1 (10.1 (6 75.0– 68.2– (3 132.9– (132.9– 150.5– (150.5–2 (1. (1.4 NCT035 INFIMH1 10. (10. 75.0 68.2 132.9 (132.9 150.5 (150.5– NCT03 75. 68. 132. (132. 150. (150.5 NCT0 (132 (150. (13 (150 (15

Abstract 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).

Abstract Background Chronic low back pain (CLBP) represents a problem in the occupational environment, often associated with disability, sick-leave demands, loss of productivity, anxiety, depression and high socioeconomic cost. The emergence of functional neuroimaging allowed new insights into brain structure and physiology in normality and chronic pain. While occupational related aspects are recognized as important risk factors for chronicity there have not been thus far evaluated by fMRI experiments. The overall objective of this study is to compare the neuronal correlates between groups of individuals CLBP with or without sick-leave demands. Methods A total of 74 individuals were divided into three groups: chronic low back pain with sick-leave demands [CLBP_L]; chronic low back pain without sick-leave demands [CLBP_NL]; individuals without pain or sick-leave demands [Control]. Functional magnetic resonance imaging was used to assess brain function during moderate acute pain stimulation task (thumb controlled pressure). Results After acute painful stimulation, a higher brain response was found in the anterior cingulate and superior and medium frontal gyrus was observed in CLBP_NL vs. CLBP_L ( p < 0,001) and increased brain response in the frontal pole and paracingulate region in control vs. CLBP_L ( p < 0.001) during acute pain stimulation. Conclusion The modulation of acute pain participates in the mechanism propagating chronic pain perception. The lower activation in the superior frontal gyrus observed in the CLBP_L group compared to CLBP_NL, reinforces the idea of an already existing activation in this area.

Abstract 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. Main body of the abstract: 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.

Resumo Peliose hepática é uma patologia benigna rara caracterizada pela presença de múltiplas cavidades preenchidas por sangue sem localização preferencial no parênquima do fígado. Pode estar relacionada a uma série de condições etiológicas, dentre elas doenças infecciosas e toxicidade por drogas imunossupressoras. Para nosso conhecimento, existem apenas três artigos que abordam a associação entre peliose hepática e lúpus eritematoso sistêmico. Neste relato, descrevemos um caso desta rara condição, destacando a importância da ressonância magnética. Uma breve revisão sobre o tema é apresentada.

Summary Peliosis hepatis is a rare benign disorder characterized by the presence of multiple cavities filled with blood with no preferential localization in the liver parenchyma. It may be related to several etiologic conditions, especially infections and toxicity of immunosuppressive drugs. To our knowledge, there are only three articles reporting the association between peliosis hepatis and systemic lupus erythematosus. In this report, we describe a case of this rare condition, highlighting the importance of magnetic resonance imaging. A short review of this subject is also presented.

OBJECTIVES: To analyse the frequency of metabolic syndrome in young adult female dermatomyositis patients and its possible association with clinical and laboratory dermatomyositis-related features and serum adipocytokines. METHOD: This cross-sectional study included 35 dermatomyositis patients and 48 healthy controls. Metabolic syndrome was defined according to the 2009 Joint Interim Statement. RESULTS: Patient age was comparable in the dermatomyositis and control groups, and the median disease duration was 1.0 year. An increased prevalence of metabolic syndrome was detected in the dermatomyositis group (34.3% vs. 6.3%; p=0.001). In addition, increased serum adiponectin and resistin levels were noted in contrast to lower leptin levels. In dermatomyositis patients, adipocytokine levels were correlated with the levels of total cholesterol, low-density cholesterol, triglycerides and muscle enzymes. A comparison of dermatomyositis patients with (n=12) and without (n=23) syndrome metabolic revealed that adipocytokine levels were also correlated with age, and that dermatomyositis patients with metabolic syndrome tended to have more disease activity despite similar adipocytokine levels. CONCLUSIONS: Metabolic syndrome is highly prevalent in young adult female dermatomyositis patients and is related to age and disease activity. Moreover, increased serum adiponectin and resistin levels were detected in dermatomyositis patients, but lower serum leptin levels were observed.

Resumo Objetivo Investigar os efeitos deletérios da exposição aos poluentes do ar na Região Metropolitana de São Paulo sobre a qualidade do sêmen de pacientes com lúpus eritematoso sistêmico (LES). Métodos Foi feito um estudo longitudinal de painel com medidas repetidas de sete anos no Laboratório de Poluição Atmosférica Experimental e Reumatologia. Foram analisadas duas amostras de sêmen de 28 pacientes com LES pós‐púberes. Foram avaliadas as concentrações diárias de exposição aos poluentes do ar PM10, SO2, NO2, ozônio e CO e variáveis meteorológicas 90 dias antes de cada data de coleta de sêmen com o uso do método de equações de estimativas generalizadas. Resultados A ciclofosfamida intravenosa (CICIV) e o ozônio estiveram associados a uma diminuição na qualidade do sêmen dos pacientes com LES. A CICIV esteve associada a um decréscimo de 64,3 milhões de espermatozoides/mL (IC 95% 39,01‐89,65; p = 0,0001) e 149,14 milhões de espermatozoides/ejaculado (IC 95% 81,93‐216,38; p = 0,017). Em relação ao ozônio, os efeitos adversos mais relevantes foram observados entre os lags (intervalo de tempo) 80 e 88, quando a exposição a uma concentração média de ozônio um intervalo interquartil maior em nove dias móveis levou a um decréscimo de 22,9 milhões de espermatozoides/mL (IC 95% 5,8‐40; p = 0,009) e 70,5 milhões de espermatozoides/ejaculado (IC 95% 12,3‐128,7; p = 0,016). Uma análise mais aprofundada dos 17 pacientes que nunca usaram CICIV mostrou associação entre a exposição ao ozônio (80‐88 dias) e o decréscimo de 30 milhões de espermatozoides/mL (IC 95% 7‐53; p = 0,011) e 79 milhões de espermatozoides/ejaculado (IC 95% 2,1‐155,9; p = 0,044). Conclusão O ozônio e a CICIV tiveram um efeito adverso consistente sobre a qualidade do sêmen de pacientes com LES durante a espermatogênese. Deve‐se considerar a minimização da exposição à poluição do ar, especialmente para pacientes com doenças inflamatórias sistêmicas crônicas que vivem nas grandes cidades.

Abstract Objective To investigate the deleterious effects of air pollutants exposure in the Sao Paulo metropolitan region on semen quality in systemic lupus erythematosus (SLE). Methods A seven-years longitudinal repeated-measures panel study was performed at the Laboratory of Experimental Air Pollution and Rheumatology Division. Two semen samples from 28 post-pubertal SLE patients were analyzed. Daily concentrations of air pollutants exposure: PM10, SO2, NO2, ozone, CO, and meteorological variables were evaluated on 90 days before each semen collection dates using generalized estimating equation models. Results Intravenous cyclophosphamide (IVCYC) and ozone had an association with a decrease in sperm quality of SLE patients. IVCYC was associated with decreases of 64.3 million of spermatozoa/mL (95% CI 39.01–89.65; p = 0.0001) and 149.14 million of spermatozoa/ejaculate (95% CI 81.93–216.38; p = 0.017). With regard to ozone, the most relevant adverse effects were observed from lags 80–88, when the exposure to an interquartile range increase in ozone 9-day moving average concentration led to decreases of 22.9 million of spermatozoa/mL (95% CI 5.8–40.0; p = 0.009) and 70.5 million of spermatozoa/ejaculate (95% CI 12.3–128.7; p = 0.016). Further analysis of 17 patients that never used IVCYC showed association between exposure to ozone (80–88 days) and decrease of 30.0 million of spermatozoa/mL (95% CI 7.0–53.0; p = 0.011) and 79.0 million of spermatozoa/ejaculate (95% CI 2.1–155.9; p = 0.044). Conclusion Ozone and IVCYC had a consistent adverse effect on semen quality of SLE patients during spermatogenesis. Minimizing exposure to air pollution should be taken into account, especially for patients with chronic systemic inflammatory diseases living in large cities.

Objetivo Elaborar recomendações para o diagnóstico, manejo e tratamento da nefrite lúpica no Brasil. Método Revisão extensa da literatura com seleção dos artigos com base na força de evidência científica e opinião dos membros da Comissão de Lúpus Eritematoso Sistêmico da Sociedade Brasileira de Reumatologia. Resultados e conclusões 1) A biópsia renal deve ser feita sempre que possível e houver indicação e quando não for possível, o tratamento deve ser orientado com base na inferência da clase histológica. 2) Devem ser implementados medidas e cuidados idealmente antes do início do tratamento, com ênfase na atenção ao risco de infecção. 3) Devem-se compartilhar riscos e benefícios do tratamento com pacientes e familiares. 4) O uso da hidroxicloroquina (preferencialmente) ou difosfato de cloroquina é recomendado para todos os pacientes (exceto contraindicação) durante as fases de indução e manutenção. 5) A avaliação da eficácia do tratamento deve ser feita com critérios objetivos de resposta (remissão completa/remissão parcial/refratariedade). 6) Os IECA e/ou BRA são recomendados como antiproteinúricos para todos os pacientes (exceto contraindicação). 7) A identificação de sinais clínicos e/ou laboratoriais sugestivos de GN laboratoriais sugestivos de glomerulonefrite proliferativa ou membranosa deve indicar início imediato de terapia específica incluindo corticosteroides e agente imunossupressor, mesmo que não seja possível comprovação histológica. 8) O tempo de uso dos imunossupressores deve ser no mínimo de 36 meses, mas eles podem ser mantidos por períodos mais longos. A sua suspensão só deve ser feita quando o paciente atingir e mantiver remissão completa sustentada. 9) Deve-se considerar nefrite lúpica refratária quando a remissão completa ou parcial não for alcançada após 12 meses de tratamento adequado, quando uma nova biópsia renal deve ser considerada para auxiliar na identificação da causa da refratariedade e decisão terapêutica.

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) Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers 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 corticosteroids 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 could 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.

Mais da metade dos pacientes com lúpus eritematoso sistêmico (LES) apresentam envolvimento cardíaco. Porém, não existem estudos de prevalência de eventos arrítmicos (EA) nesta doença, nem de correlações laboratoriais preditoras de sua ocorrência. É possível que o clássico segundo pico de mortalidade da doença esteja relacionado com a ocorrência da EA, sobretudo pela natureza súbita dos óbitos relatados. Processo autoimune, complicações ateroscleróticas e, até mesmo, efeito adverso do tratamento (cardiotoxicidade pela cloroquina) parecem ser os mecanismos fisiopatológicos mais prováveis para estes distúrbios. A participação direta de autoanticorpos, como o anti-Ro/SSA e o anti-RNP ainda é controversa.Todos os tipos de bloqueios atrioventriculares (BAV), distúrbios da condução intraventricular e a doença do nó sinusal já foram descritos na doença. As taquicardias mais identificadas são a taquicardia sinusal, a fibrilação atrial e as extrassístoles atriais. O prolongamento do intervalo QT e a presença de potenciais tardios ao eletrocardiograma de alta resolução também já foram documentados em pacientes com LES e podem estar associados a maiores taxas de mortalidade. A toxicidade cardíaca secundária ao uso de cloroquina poderia determinar diversos tipos de EA. Entretanto, existem poucos relatos de bloqueio fascicular que poderiam evoluir para BAVT com o uso desta droga. Uma vez que estes efeitos adversos são raramente descritos, os benefícios das propriedades anti-inflamatórias e imunes reforçam o uso dos antimaláricos nesta doença. Uma avaliação cardiológica completa deve incluir exames do sistema excito-condutor e deve ser realizada em todos os pacientes com LES no sentido de identificar EA, prevenindo sintomas e até mesmo a morte súbita.

Cardiac involvement is present in more than half of the patients with Systemic Lupus Erythematosus (SLE). However, studies on the prevalence of arrhythmias in this disease and laboratorial correlations predictive of their development do not exist. It seems possible that the classic second mortality peak is related to arrhythmias, mainly due to the sudden nature of those deaths. Autoimmune process, atherosclerotic complications, and even adverse effects secondary to the treatment of this disorder (chloroquine cardiotoxicity) seem to be the main pathophysiological mechanisms of those disturbances. The direct participation of autoantibodies, such as anti-Ro/SSA and anti-RNP, is still controversial. All types of AV blocks (AVB), intraventricular conduction disturbances, and sick sinus syndrome have already been described in this disease. Tachycardias identified more often include sinus tachycardia, atrial fibrillation, and atrial ectopies. Long QT syndrome and the presence of late potentials in signal-averaged ECG have also been described in SLE patients and they can be associated with increased mortality rates. Cardiac toxicity secondary to chloroquine could be responsible for several types of arrhythmias. However, few cases of fascicular block evolving to complete AV block have been described. Since these adverse effects are rarely reported, the beneficial anti-inflammatory and immune properties support the use of antimalarials in this disease. A complete cardiologic evaluation should include the conduction system and must be carried out in all SLE patients to identify arrhythmias, therefore preventing symptoms and also sudden cardiac death.

INTRODUÇÃO: A ecocardiografia bidimensional é um método de diagnóstico por imagem não invasivo que avalia, de modo eficaz, a função diastólica global e regional do ventrículo esquerdo. O comprometimento da função diastólica ventricular esquerda no lúpus eritematoso sistêmico (LES) é quase sempre silencioso, sugerindo um estado subclínico de disfunção diastólica. OBJETIVO: Este estudo tem por finalidade demonstrar as diversas técnicas ecocardiográficas para a aferição da função diastólica no LES. PACIENTES E MÉTODOS: Foram avaliadas consecutivamente 50 pacientes com LES e 50 controles do sexo feminino, pareadas por sexo e idade. Os exames foram realizados por dois observadores independentes cujos resultados tiveram concordância. RESULTADOS: Não houve diferença significativa da função diastólica global do ventrículo esquerdo entre os grupos, exceto pelo método da velocidade de propagação do fluxo mitral (Vp), que evidenciou diminuição da velocidade de enchimento rápido nas pacientes com LES. Foi detectado maior comprometimento da função diastólica regional nas pacientes com LES, na protodiástole, à altura do anel mitral, mais evidente na porção basal do septo interventricular. CONCLUSÃO: No LES, a disfunção diastólica do ventrículo esquerdo pode ser constatada através da avaliação do Doppler tissular na região do anel mitral e pela velocidade de propagação do fluxo mitral.

INTRODUCTION: Bidimensional echocardiography is a non-invasive imaging diagnostic method that effectively assesses global and regional left ventricular diastolic function. Disruption of left ventricular diastolic function in systemic lupus erythematosus (SLE) is almost always clinically silent, suggesting a subclinical diastolic dysfunction. OBJECTIVE: We evaluate in the the present study the different echocardiographic techniques available to assess the diastolic dysfunction in SLE. PATIENTS AND METHODS: Fifty consecutive SLE patients and 50 healthy females, matched by gender and age, were evaluated. Exams were conducted by two independent observers whose results showed concordance. RESULTS: Significant differences in global left ventricular diastolic function between both groups, except for mitral flow propagation velocity (Vp), which showed a reduction in rapid filling in SLE patients, were not observed. Greater involvement of regional diastolic function, in protodiastole, at the level of the mitral ring, especially in the basal area of the interventricular septum, was observed. CONCLUSION: Left ventricular diastolic dysfunction in SLE patients can be identified by tissue Doppler of the mitral ring and by mitral flow propagation velocity.

OBJETIVOS: Avaliar diferentes métodos diagnósticos para a avaliação de pacientes portadores de lúpus eritematoso sistêmico, usuários crônicos do difosfato de cloroquina (DFC) e, portanto, com alto risco para retinopatia tóxica. MÉTODOS: Foram analisados 72 olhos de 36 pacientes consecutivos, seguidos no Serviço de Reumatologia do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, de julho de 2007 a abril de 2008. Dados demográficos e clínicos foram avaliados com o intuito de estudar os fatores de alto risco e comparar os seguintes métodos oftalmológicos: acuidade visual, biomicroscopia da córnea, biomicroscopia do fundo, retinografia, angiofluoresceinografia da retina, campo visual macular com mira branca. RESULTADOS: Dos 36 pacientes, 34 (94,4%) eram mulheres. A média de idade foi 39,9 ± 9,8 anos, com tempo de doença igual a 13,9 ± 6,6 anos. Além do uso crônico da cloroquina, os pacientes apresentaram altas doses diárias (>3 mg/kg) e cumulativas. Não foi observada relação entre estes fatores de alto risco e maior prevalência de retinopatia. Foi encontrada prevalência de retinopatia igual a 38,9%, confirmada por alterações bilaterais, centrais ou paracentrais e reprodutíveis no exame de campo visual. Outros exames indicados para seguimento, como acuidade visual, biomicroscopia de fundo e angiofluoresceinografia não foram capazes de diagnosticar a maioria das alterações confirmadas pelo campo visual. CONCLUSÃO: Foi observada alta prevalência de retinopatia por cloroquina entre os pacientes com alto risco, usuários crônicos do DFC, segundo os achados do campo visual. A avaliação desses pacientes deve considerar a realização do exame de campo visual em intervalos menores que os propostos, mesmo quando não há suspeita clínica.

PURPOSE: To evaluate different diagnostic methods for high risk chloroquine retinopathy due to prolonged use of chloroquine (more than 5 years) by systemic lupus erythematosus patients. Methods: Seventy-two eyes of 36 consecutive patients, followed in the Division of Rheumatology, School of Medicine, University of São Paulo, were analyzed from July 2007 to April 2008. Demographic and clinical data were evaluated in order to study risk factors and to compare the following different ophthalmological methods: visual acuity, biomicroscopy, fundus examination, retinography, fluorescein angiogram, visual field test and, color vision tests. RESULTS: From 36 patients, 34 (94.4%) were female. The mean age was 39.9 ± 9.8 years and the disease duration was 13.9 ± 6.6 years. Besides chronic use of chloroquine, patients also showed high daily and cumulative doses. These high risk factors were not related to a higher retinopathy prevalence. Visual field showed 38.9% of retinopathy prevalence. Other ophthalmological methods failed in detecting most cases. CONCLUSION: High prevalence of retinopathy in high risk patients was observed by visual field test, but other ophthalmological methods failed in detecting alterations. Ophthalmological assessment of these patients should include visual field, even in the absence of clinical alterations.

OBJETIVO: Avaliar a saúde reprodutiva em homens com lúpus eritematoso sistêmico (LES) e compará-la com controles saudáveis. MÉTODOS: Vinte e cinco pacientes com LES do sexo masculino foram avaliados com dados demográficos, exame urológico (incluindo parâmetros pubertários e função sexual/erétil), ultrassonografia testicular com Doppler, perfil hormonal, análise seminal, características clínicas e tratamento. O grupo-controle incluiu 25 homens saudáveis. RESULTADOS: A mediana da idade atual foi similar nos pacientes com LES comparada aos controles (26 versus 27 anos, P = 0,756). As frequências de disfunções sexual/erétil foram significativamente maiores nos pacientes com LES em relação aos controles (20% versus 0%, P = 0,0001) e o número de gestações espontâneas foi menor (20% versus 60%, P = 0,0086). Uma tendência de uso infrequente de contraceptivos foi observada em pacientes com LES comparada aos controles (48% versus 76%, P = 0,079). Além disso, as frequências de parâmetros de disfunção gonadal: atrofia testicular avaliada pela ultrassonografia (36% versus 8%, P = 0,037), níveis elevados de FSH e/ou LH (36% versus 0%, P = 0,002) e alterações dos espermatozoides (48% versus 0%, P = 0,0001) foram estatisticamente maiores nos pacientes com LES versus controles. Os pacientes com LES e disfunção sexual/erétil não realizaram atividade sexual no último mês versus 95% dos pacientes sem disfunção (P = 0,0001). Entretanto, nenhuma diferença foi evidenciada nos pacientes com LES com e sem disfunção sexual/erétil em relação a dados demográficos, atividade da doença, dano cumulativo e tratamento. CONCLUSÃO: Este é o primeiro estudo que identificou disfunção sexual/erétil e gonadal em homens lúpicos. Uma abordagem multidisciplinar é essencial para oferecer medidas preventivas para esses pacientes.

OBJECTIVE: To assess reproductive health in male systemic lupus erythematosus (SLE) patients and compare them with controls. METHODS: Twenty-five male SLE patients were evaluated for demographic data, urologic evaluation (including pubertal parameters, sexual/erectile function), testicular Doppler ultrasound, hormone profile, semen analysis, clinical features and treatment. The control group included 25 healthy men. RESULTS: The current median age was similar in SLE patients compared with controls (26 versus 27 years, P = 0.756). The frequencies of sexual/erectile disfunction were significantly higher (20% versus 0%, P = 0.0001) and the number of spontaneous pregnancies were lower in SLE patients than in controls (20% versus 60%, P = 0.0086). A trend to low contraceptive use was observed in SLE patients compared with controls (48% versus 76%, P = 0.079). Moreover, the frequencies of gonadal dysfunction parameters, such as testicular atrophies measured by ultrasound (36% versus 8%, P = 0.037), elevated FSH and/or LH levels (36% versus 0%, P = 0.002), and sperm abnormalities (48% versus 0%, P = 0.0001), were statistically higher in SLE patients versus controls. SLE patients with sexual/erectile disfunction had no sexual activity in the last month versus 95% of SLE patients without dysfunction (P = 0.0001). On the other hand, no differences were evidenced in SLE patients with or without sexual/erectile disfunction according to demographic data, disease activity, cumulative damage and treatment. CONCLUSION: This is the first study to identify sexual/erectile and gonadal disfunction in male SLE patients. A multidisciplinary approach is essential in order to offer preventive measures for these patients.