ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the “per protocol” population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization’s (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size. Background 201 COVID19 COVID 19 (COVID-19 populations useful Herein IL6, IL6 IL 6, 6 (IL)-6 IL17, IL17 17, 17 IL2, IL2 2, 2 COVID19. 19. Methods multicenter openlabel, openlabel open label, label open-label prospective Brazil moderatetocritical moderate critical COVID-1 (SOC) IL-1 ixekizumab SC/week SCweek SC week lowdose low IL- 1.5 15 5 (1. discharge (colchicine 05 0 (0. 0. 2x/day 2xday xday 2x x alone protocol Organizations Organization s (WHO sevencategory seven category 28 Results Interestingly group observed Conclusions Ixekizumab treatment size 20 COVID1 (COVID-1 (IL)- IL1 COVID- (SOC 1. (1 (0 (COVID- (IL) ( (COVID (IL

Abstract Introduction Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. Objective To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. Method Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann–Whit-ney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). Results 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) (‘p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. Conclusions ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development. (RA extraarticular extra articular (ExtRA time cohort Crosssectional Cross sectional study multicentric multi centric 1 1987 (198 201 ACREULAR. ACREULAR ACR EULAR . ACR-EULAR) 082015, 082015 08 2015, 2015 08-2015 record Mann–Whitney MannWhitney Mann–Whit ney Mann Whit Utest, Utest U U-test Fishers Fisher s chisquare chi square appropriate 5 p 0.05. 005 0.05 0 05 0.05) 111 included 89 women mean SD 582 58 2 58. 115 11. years 145 14 14. 122 12 12. RF, (RF 1108 77 77% anticyclic anti cyclic ACPA, ACPA (ACPA 477 78 78% 33 26 234 23 4 23.4 NonExtRA Non 0.001, 0001 0.001 , 001 0.018, 0018 0.018 018 0.018) CDAI (CDAI DAS HAQ (HAQ group 0.002, 0002 0.002 002 0.002) 0.049 0049 049 GC (GC ‘p nonsteroidal non steroidal antiinflammatory NSAIDs (NSAIDs underestimated longterm long term development 198 (19 20 ACR-EULAR 08201 08-201 Whitney MannWhit 00 0.0 8 110 7 47 3 23. 000 0.00 0.01 01 0.04 004 04 19 (1 0820 08-20 0. ( 082 08-2 08-

Abstract Background Management delays imply worse outcomes in rheumatoid arthritis (RA) and, therefore, should be minimized. We evaluated changes in diagnostic and treatment delays regarding RA in the last decades in Brazil. Methods Adults fulfilling the ACR/EULAR (2010) criteria for RA were assessed. Delays in diagnosis and treatment, and the frequencies of early management initiation within thresholds (windows of opportunity) of 3, 6, and 12 months from symptoms onset were evaluated. The Mann–Kendall trend test, chi-squared tests with Cramer’s V effect sizes and analysis of variance were conducted. Results We included 1116 patients: 89.4% female, 56.8% white, mean (SD) age 57.1 (11.5) years. A downward trend was found in diagnostic (tau = - 0.677, p < 0.001) and treatment (tau = - 0.695, p < 0.001) delays from 1990 to 2015. The frequency of early management increased throughout the period, with ascending effect sizes across the 3-, 6-, and 12-month windows (V = 0.120, 0.200 and 0.261, respectively). Despite all improvements, even in recent years (2011–2015) the diagnostic and treatment delays still remained unacceptably high [median (IQR): 8 (4–12) and 11 (5–17) months, respectively], with only 17.2% of the patients treated within the shortest, 3-month window. Conclusion The delays in diagnosis and treatment of RA decreased during the last decades in Brazil. Improvements (effect sizes) were greater at eliminating extreme delays (≥ 12 months) than in attaining really short management windows (≤ 3 months). Very early treatment was still an unrealistic goal for most patients with RA. (RA therefore minimized Brazil ACREULAR ACR EULAR 2010 (2010 assessed opportunity 6 1 MannKendall Mann Kendall test chisquared chi squared Cramers Cramer s conducted 111 894 89 4 89.4 female 568 56 56.8 white SD (SD 571 57 57. 11.5 115 5 (11.5 tau 0677 0 677 0.677 0.001 0001 001 0695 695 0.695 199 2015 period , 3- 6- 12month month 0120 120 0.120 0200 200 0.20 0261 261 0.261 respectively. respectively . respectively) improvements 2011–2015 20112015 2011 (2011–2015 median IQR (IQR) 4–12 412 (4–12 5–17 517 17 (5–17 respectively, respectively] 172 2 17.2 shortest 3month window ≥ ( ≤ months. 201 (201 89. 56. 11. (11. 067 67 0.67 0.00 000 00 069 69 0.69 19 012 0.12 020 20 0.2 026 26 0.26 2011–201 2011201 (2011–201 (IQR 4–1 41 (4–1 5–1 51 (5–1 17. (20 (11 06 0.6 0.0 01 0.1 02 0. 2011–20 201120 (2011–20 4– (4– 5– (5– (2 (1 2011–2 20112 (2011–2 (4 (5 2011– (2011– (2011

Abstract Background Early rheumatoid arthritis (RA) offers an opportunity for better treatment outcomes. In real-life settings, grasping this opportunity might depend on access to specialized care. We evaluated the effects of early versus late assessment by the rheumatologist on the diagnosis, treatment initiation and long-term outcomes of RA under real-life conditions. Methods Adults meeting the ACR/EULAR (2010) or ARA (1987) criteria for RA were included. Structured interviews were conducted. The specialized assessment was deemed “early” when the rheumatologist was the first or second physician consulted after symptoms onset, and “late” when performed afterwards. Delays in RA diagnosis and treatment were inquired. Disease activity (DAS28-CRP) and physical function (HAQ-DI) were evaluated. Student's t, Mann-Whitney U, chi-squared and correlation tests, and multiple linear regression were performed. For sensitivity analysis, a propensity score-matched subsample of early- vs. late-assessed participants was derived based on logistic regression. The study received ethical approval; all participants signed informed consent. Results We included 1057 participants (89.4% female, 56.5% white); mean (SD) age: 56.9 (11.5) years; disease duration: 173.1 (114.5) months. Median (IQR) delays from symptoms onset to both RA diagnosis and initial treatment coincided: 12 (6–36) months, with no significant delay between diagnosis and treatment. Most participants (64.6%) first sought a general practitioner. Notwithstanding, 80.7% had the diagnosis established only by the rheumatologist. Only a minority (28.7%) attained early RA treatment (≤ 6 months of symptoms). Diagnostic and treatment delays were strongly correlated (rho 0.816; p < 0.001). The chances of missing early treatment more than doubled when the assessment by the rheumatologist was belated (OR 2.77; 95% CI: 1.93, 3.97). After long disease duration, late-assessed participants still presented lower chances of remission/low disease activity (OR 0.74; 95% CI: 0.55, 0.99), while the early-assessed ones showed better DAS28-CRP and HAQ-DI scores (difference in means [95% CI]: −0.25 [−0.46, −0.04] and − 0.196 [−0.306, −0.087] respectively). The results in the propensity-score matched subsample confirmed those observed in the original (whole) sample. Conclusions Early diagnosis and treatment initiation in patients with RA was critically dependent on early access to the rheumatologist; late specialized assessment was associated with worse long-term clinical outcomes. (RA reallife real life settings care longterm term conditions ACREULAR ACR EULAR 2010 (2010 1987 (1987 conducted “early “late afterwards inquired DAS28CRP DASCRP DAS28 CRP DAS (DAS28-CRP HAQDI HAQ DI (HAQ-DI Students Student s t MannWhitney Mann Whitney U chisquared chi squared tests analysis scorematched score vs lateassessed assessed approval consent 105 89.4% 894 89 4 (89.4 female 565 56 5 56.5 white white) SD (SD age 569 9 56. 11.5 115 11 (11.5 years duration 1731 173 1 173. 114.5 1145 114 (114.5 IQR (IQR coincided 6–36 636 36 (6–36 64.6% 646 64 (64.6% practitioner Notwithstanding 807 80 7 80.7 28.7% 287 28 (28.7% ≤ ( symptoms. . symptoms) rho 0.816 0816 0 816 0.001. 0001 0.001 001 0.001) OR 2.77 277 2 77 95 CI 193 93 1.93 3.97. 397 3.97 3 97 3.97) remissionlow remission low 0.74 074 74 055 55 0.55 0.99, 099 0.99 , 99 0.99) earlyassessed difference [95 CI] 025 25 −0.2 −0.46, 046 46 [−0.46 −0.04 004 04 0196 196 0.19 −0.306, 0306 306 [−0.306 −0.087 0087 087 respectively. respectively respectively) propensityscore whole (whole sample 201 (201 198 (198 DAS2 10 89.4 8 (89. 11. (11. 17 114. (114. 6–3 63 (6–3 64.6 (64.6 80. 28.7 (28.7 0.81 081 81 000 0.00 00 2.7 27 19 1.9 39 3.9 0.7 07 05 0.5 09 0.9 [9 02 −0. −0.46 [−0.4 −0.0 019 0.1 −0.306 030 30 [−0.30 −0.08 008 08 20 (20 (19 89. (89 (11 (114 6– (6– 64. (64. 28. (28. 0.8 0.0 2. 1. 3. 0. [ −0 −0.4 [−0. 01 −0.30 03 [−0.3 (2 (1 (8 (6 (64 (28 [−0 −0.3 [−

Abstract Introduction In chronic arthropathies, there are several mechanisms of joint destruction. In recent years, studies have reported the implication of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) in the process of activation and differentiation of osteoclasts, a key cell in the development of bone erosion. The RANKL/OPG ratio is increased in the serum of patients with malignant diseases and lytic bone disease, as well as rheumatoid arthritis (RA). The objective of this study was to measure and compare the concentrations of OPG and RANKL in the synovial fluid (SF) of patients with rheumatoid arthritis, spondyloarthritis (SpA) and osteoarthritis (OA). Methods This was an observational and cross-sectional study with 83 patients, 33 with RA, 32 with SpA and 18 with OA, followed up regularly in the outpatient clinics of the Rheumatology Department of the Clinics Hospital of the Ribeirão Preto Medical School-USP. All patients were assessed for indications for arthrocentesis by the attending physicians at the time of SF collection and were evaluated for demographic variables and medication use. Disease activity was assessed in individuals with RA and SpA. The quantification of SF OPG and RANKL levels was performed by ELISA, and the correlations of the results with clinical, laboratory and radiological parameters were assessed. Results We found no statistically significant difference in the RANKL and OPG levels among the groups. Patients with RA showed a positive correlation between the SF cell count and RANKL level (r = 0.59; p < 0.05) and the RANKL/ OPG ratio (r = 0.55; p < 0.05). Patients with OA showed a strong correlation between C-reactive protein (CRP) and the RANKL/OPG ratio (r = 0.82; p < 0.05). There was no correlation between the OPG and RANKL levels and markers of inflammatory activity or the disease activity index in patients with RA or SpA. Conclusion Within this patient cohort, the RANKL/OPG ratio was correlated with the SF cell count in patients with RA and with serum CRP in patients with OA, which may suggest a relationship with active inflammation and more destructive joint disease. arthropathies destruction years kappaB kappa B (RANKL (OPG osteoclasts erosion RANKLOPG RA. . (RA) (SF (SpA OA. (OA) crosssectional cross sectional 8 3 1 SchoolUSP. SchoolUSP School USP. USP School-USP use ELISA clinical groups r 0.59 059 0 59 0.05 005 05 0.55 055 55 0.05. Creactive C reactive (CRP 0.82 082 82 cohort (RA (OA 0.5 5 0.0 00 0.8 08 0.

Abstract Background: Rheumatoid arthritis (RA) is a common autoimmune systemic inflammatory disease. In addition to joint involvement, RA patients frequently have other comorbidities, such as cardiovascular diseases. Drugs used for RA treatment may increase or decrease the risk of a cardiovascular event. This study aims to analyze cardiovascular risk comorbidities in patients with RA and the correlation with the use of anti-rheumatic drugs. Methods: Cross-sectional study conducted based on the real-life rheumatoid arthritis study database - REAL, a prospective observational cohort study. Associations between the use of anti-rheumatic drugs and the presence of comorbidities were represented by their prevalence ratio and evaluated using the Chi-square or Fisher’s Exact tests. Results: We assessed 1116 patients, 89.4% women, mean age of 55.15 years and predominance of seropositive disease. 63.3% had some cardiovascular comorbidity, predominantly hypertension (49.9%). The use of glucocorticoids was observed in 47.4% of patients and there was a significant tendency of lower use of these drugs in the presence of dyslipidemia (PR: 0.790; p = 0.007). We observed that the presence of cardiovascular comorbidities was associated with higher use of bDMARDs (PR:1.147; p = 0.003). Conclusions: The presence of cardiovascular risk comorbidities was confirmed to be higher in RA patients. Different treatment strategies using less glucocorticoids in the presence of dyslipidemia and more common use of bDMARDs in patients with cardiovascular comorbidities suggest that rheumatologists are aware of the potential influence of the DMARDs in the risk of cardiovascular event. Reinforcing these results, we highlight the need for a better baseline assessment to guide the choice of anti-rheumatic drugs in RA patients who have comorbidities.

Abstract Rheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.

Abstract Background: There are few data on the epidemiology, clinical manifestations and management of RA in Brazil, even with the recognition of the high direct, indirect and societal costs of this disease. Herein, we report the formation of the REAL - Rheumatoid Arthritis in Real Life, the first nationally representative multicenter prospective observational study in Brazil. Methods: The REAL study was designed to include a total of 1300 evaluable patients from 13 tertiary care public health centers specialized in RA management and representative of 5 regions of Brazil. Each center was expected to enroll ~ 100 consecutively seen patients and follow them prospectively in a systematic protocol-driven fashion with scheduled visits at baseline, 6 and 12 months. Core clinical, laboratory and patient-reported outcomes measures were required to be collected at each visit. Results: A total of 1115 patients (89.4% female, mean age of 56.7 years and median disease duration of 12.7 years) were enrolled from 11 participating centers. Almost 80% of patients were of middle-low or low socioeconomic classes. The median educational time was 8 years, with 3.23% being below literacy level. The interval between symptoms and diagnosis varied from 1 to 457 months (median 12 months). Almost half of the patients were on glucocorticoids, 96.5% on DMARDs, with 35.7% on biologics. Median HAQ-DI was 0.875, ranging from 0 to 3. Median DAS28-ESR was 3.5, with 58.7% of patients presenting moderate or high disease activity. Conclusions: The first large cohort of Brazilian patients with RA in a real-life setting shows several striking differences from previously published cohorts from other countries. The long delay for diagnosis and start of DMARDs may partly explain the high frequency of erosive disease. An elevated percentage of patients on moderate or high disease activity was seen, despite of the high frequency of corticosteroid and biologics utilization. Data from this cohort may enable public health managers of developing countries better allocate the limited resources available for the care of RA patients.

Abstract The objective of this document is to provide a comprehensive update of the recommendations of Brazilian Society of Rheumatology on drug treatment of rheumatoid arthritis (RA), based on a systematic literature review and on the opinion of a panel of rheumatologists. Four general principles and eleven recommendations were approved. General principles: RA treatment should (1) preferably consist of a multidisciplinary approach coordinated by a rheumatologist, (2) include counseling on lifestyle habits, strict control of comorbidities, and updates of the vaccination record, (3) be based on decisions shared by the patient and the physician after clarification about the disease and the available therapeutic options; (4) the goal is sustained clinical remission or, when this is not feasible, low disease activity. Recommendations: (1) the first line of treatment should be a csDMARD, started as soon as the diagnosis of RA is established; (2) methotrexate (MTX) is the first-choice csDMARD; (3) the combination of two or more csDMARDs, including MTX, may be used as the first line of treatment; (4) after failure of first-line therapy with MTX, the therapeutic strategies include combining MTX with another csDMARD (leflunomide), with two csDMARDs (hydroxychloroquine and sulfasalazine), or switching MTX for another csDMARD (leflunomide or sulfasalazine) alone; (5) after failure of two schemes with csDMARDs, a bDMARD may be preferably used or, alternatively a tsDMARD, preferably combined, in both cases, with a csDMARD; (6) the different bDMARDs in combination with MTX have similar efficacy, and therefore, the therapeutic choice should take into account the peculiarities of each drug in terms of safety and cost; (7) the combination of a bDMARD and MTX is preferred over the use of a bDMARD alone; (8) in case of failure of an initial treatment scheme with a bDMARD, a scheme with another bDMARD can be used; in cases of failure with a TNFi, a second bDMARD of the same class or with another mechanism of action is effective and safe; (9) tofacitinib can be used to treat RA after failure of bDMARD; (10) corticosteroids, preferably at low doses for the shortest possible time, should be considered during periods of disease activity, and the risk-benefit ratio should also be considered; (11) reducing or spacing out bDMARD doses is possible in patients in sustained remission.

O tratamento das doenças reumáticas autoimunes sofreu uma progressiva melhora ao longo da última metade do século passado, que foi expandida com a contribuição das terapias biológicas ou imunobiológicos. No entanto, há que se atentar para as possibilidades de efeitos indesejáveis advindos da utilização dessa classe de medicações. A Sociedade Brasileira de Reumatologia (SBR) elaborou um documento, baseado em ampla revisão da literatura, sobre os aspectos relativos à segurança dessa classe de fármacos, mais especificamente no que diz respeito ao tratamento da artrite reumatoide (AR) e das espondiloartrites. Os temas selecionados pelos especialistas participantes, sobre os quais foram estabelecidas considerações quanto à segurança do uso de drogas biológicas, foram: ocorrência de infecções (bacterianas, virais, tuberculose), reações infusionais, reações hematológicas, neurológicas, gastrointestinais, cardiovasculares, ocorrências neoplásicas (neoplasias sólidas e da linhagem hematológica), imunogenicidade, outras ocorrências e reposta vacinal. Optou-se, por motivos didáticos, por se fazer um resumo da avaliação de segurança, de acordo com os tópicos anteriores, por classe de drogas/mecanismo de ação (antagonistas do fator de necrose tumoral, bloqueador da co-estimulação do linfócito T, depletor de linfócito B e bloqueador do receptor de interleucina-6). Em separado, foram tecidas considerações gerais sobre segurança do uso de biológicos na gravidez e na lactação. Esta revisão procura oferecer uma atualização ampla e equilibrada das experiências clínica e experimental acumuladas nas últimas duas décadas de uso de medicamentos imunobiológicos para o tratamento da AR e espondiloartrites.

The treatment of autoimmune rheumatic diseases has gradually improved over the last half century, which has been expanded with the contribution of biological therapies or immunobiopharmaceuticals. However, we must be alert to the possibilities of undesirable effects from the use of this class of medications. The Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia) produced a document based on a comprehensive literature review on the safety aspects of this class of drugs, specifically with regard to the treatment of rheumatoid arthritis and spondyloarthritides. The themes selected by the participating experts, on which considerations have been established as the safe use of biological drugs, were: occurrence of infections (bacterial, viral, tuberculosis), infusion reactions, hematological, neurological, gastrointestinal and cardiovascular reactions, neoplastic events (solid tumors and hematologic neoplasms), immunogenicity, other occurrences and vaccine response. For didactic reasons, we opted by elaborating a summary of safety assessment in accordance with the previous themes, by drug class/mechanism of action (tumor necrosis factor antagonists, T-cell co-stimulation blockers, B-cell depletors and interleukin-6 receptor blockers). Separately, general considerations on safety in the use of biologicals in pregnancy and lactation were proposed. This review seeks to provide a broad and balanced update of that clinical and experimental experience pooled over the last two decades of use of immunobiological drugs for RA and spondyloarthritides treatment.

A síndrome do anticorpo antifosfolípide (SAF) é uma trombofilia autoimune, caracterizada pela presença de anticorpos plasmáticos contra fosfolípides, associada a episódios recorrentes de trombose venosa e/ou arterial e morbidade gestacional (especialmente abortamento de repetição). Reportamos o caso de uma paciente feminina, jovem, com diagnóstico de lúpus eritematoso sistêmico (LES), associado à presença de anticorpos antifosfolípide de longa data, com apresentação de infarto agudo do miocárdio (IAM) por trombose proximal da artéria descendente anterior como primeira complicação clínica da SAF.

The antiphospholipid syndrome (APS) is an autoimmune thrombophilia, characterized by the presence of plasma antibodies against phospholipids, associated with recurrent episodes of venous and/or arterial thrombosis and gestational morbidity (especially recurrent miscarriage). We report the case of a young female patient diagnosed with systemic lupus erythematosus (SLE) associated with the presence of antiphospholipid antibodies for a long time, presenting with acute myocardial infarction (AMI) due to proximal thrombosis of the anterior descending artery as the first clinical complication of APS.

El Síndrome del Anticuerpo Antifosfolípido (SAF), es una trombofilia autoinmune, caracterizada por la presencia de anticuerpos plasmáticos contra fosfolípidos, asociada a episodios recurrentes de trombosis venosa y/o arterial y morbilidad gestacional (especialmente aborto de repetición). Reportamos aquí, el caso de una paciente del sexo femenino, joven, con diagnóstico de lupus eritematoso sistémico (LES), asociado a la presencia de anticuerpos antifosfolípido hacía ya mucho tiempo, presentando infarto agudo del miocardio (IAM), por trombosis proximal de la arteria descendente anterior como primera complicación clínica de la SAF.

OBJETIVO: Elaborar recomendações para o tratamento da artrite reumatoide no Brasil. MÉTODO: Revisão da literatura com seleção de artigos baseados em evidência e opinião de especialistas da Comissão de Artrite Reumatoide da Sociedade Brasileira de Reumatologia. RESULTADOS E CONCLUSÕES: 1) A decisão terapêutica deve ser compartilhada com o paciente; 2) imediatamente após o diagnóstico, uma droga modificadora do curso da doença (DMCD) deve ser prescrita e o tratamento ajustado para atingir remissão; 3) o tratamento deverá ser conduzido por reumatologista; 4) o tratamento inicial inclui DMCD sintéticas; 5) o metotrexato é a droga de escolha; 6) pacientes que não alcançaram resposta após a utilização de dois esquemas de DMCD sintéticas devem ser avaliados para DMCD biológicas; 7) excepcionalmente, DMCD biológicas poderão ser consideradas mais precocemente; 8) recomenda-se preferencialmente o uso de agentes anti-TNF como terapia biológica inicial; 9) após falha terapêutica a uma primeira DMCD biológica, outros biológicos poderão ser utilizados; 10) ciclofosfamida e azatioprina podem ser consideradas em manifestações extra-articulares graves; 11) recomenda-se a utilização de corticoide oral em baixas doses e por curtos períodos; 12) os anti-inflamatórios não hormonais devem sempre ser prescritos em associação à DMCD; 13) avaliações clínicas devem ser mensais no início do tratamento; 14) terapia física, reabilitação e terapia ocupacional são indicadas; 15) deve-se recomendar tratamento cirúrgico para correção de sequelas; 16) métodos de terapia alternativa não substituem a terapia tradicional; 17) deve-se orientar planejamento familiar; 18) orienta-se a busca ativa e o manejo de comorbidades; 19) atualizar e documentar a vacinação do paciente; 20) doenças transmissíveis endêmico-epidêmicas devem ser investigadas e tratadas.

OBJECTIVE: To elaborate recommendations for the treatment of rheumatoid arthritis in Brazil. METHOD: Literature review with articles' selection based on evidence and the expert opinion of the Rheumatoid Arthritis Committee of the Brazilian Society of Rheumatology. RESULTS AND CONCLUSIONS: 1) The therapeutic decision should be shared with the patient; 2) immediately after the diagnosis, a disease-modifying antirheumatic drug (DMARD) should be prescribed, and the treatment adjusted to achieve remission; 3) treatment should be conducted by a rheumatologist; 4) the initial treatment includes synthetic DMARDs; 5) methotrexate is the drug of choice; 6) patients who fail to respond after two schedules of synthetic DMARDs should be assessed for the use of biologic DMARDs; 7) exceptionally, biologic DMARDs can be considered earlier; 8) anti-TNF agents are preferentially recommended as the initial biologic therapy; 9) after therapeutic failure of a first biologic DMARD, other biologics can be used; 10) cyclophosphamide and azathioprine can be used in severe extra-articular manifestations; 11) oral corticoid is recommended at low doses and for short periods of time; 12) non-steroidal anti-inflammatory drugs should always be prescribed in association with a DMARD; 13) clinical assessments should be performed on a monthly basis at the beginning of treatment; 14) physical therapy, rehabilitation, and occupational therapy are indicated; 15) surgical treatment is recommended to correct sequelae; 16) alternative therapy does not replace traditional therapy; 17) family planning is recommended; 18) the active search and management of comorbidities are recommended; 19) the patient's vaccination status should be recorded and updated; 20) endemic-epidemic transmissible diseases should be investigated and treated

OBJETIVO: Traçar um perfil clínico e laboratorial da síndrome do antifosfolípide (SAF), comparando a primária (SAFP) com aquela secundária (SAFS) ao lúpus eritematoso sistêmico (LES). MÉTODOS: Avaliamos 27 pacientes com SAFP e 32 com SAFS ao LES, acompanhados no Ambulatório de Colagenoses do HC/FMRP/ USP, quanto à ocorrência de trombose arterial, venosa, perda gestacional, livedo reticular, fenômeno de Raynaud, anemia hemolítica auto-imune, plaquetopenia, linfopenia, anticorpos anticardiolipina, anticoagulante lúpico, antinucleares, anti-Sm e VDRL. Os anticorpos anticardiolipina e anti-Sm foram pesquisados por ELISA, os antinucleares por imunofluorescência indireta e o anticoagulante lúpico pelo tempo de protrombina diluída, tempo de coagulação do caulin ou tempo do veneno de víbora de Russell diluído. Para análise estatística utilizamos o teste exato de Fisher bicaudal. RESULTADOS: Observamos aumento da freqüência de trombose arterial na SAFP (59,3% vs 25,0%, p=0,009) e de trombose venosa na SAFS (53,1% vs 33,3%, p>0,05), enquanto não houve diferenças entre as freqüências de perda gestacional (50,0% vs 56,7%), fenômeno de Raynaud (18,5% vs 18,8%), livedo reticular (18,5% vs12,5%), anticoagulante lúpico (33,3% vs 37,5%) e anticardiolipina IgG (79,2% vs 72,4%) e IgM (58,4% vs 65,5%). Ademais, observamos aumento significante de linfopenia (71,2% vs 7,4%, p<0,0001), de anticorpos antinucleares (100% vs 7,4%, p<0,0001) e de VDRLpositivo (47,1% vs 5,0%, p=0,005) na SAFS ao LES quando comparada com a SAFP. CONCLUSÕES: As manifestações clínicas e laboratoriais são semelhantes na SAFP e na SAFS ao LES, sendo a trombose arterial mais comum na SAFP, enquanto a presença de linfopenia, anticorpos antinucleares e VDRL positivo está associada com a SAFS ao LES.

OBJECTIVE: To study clinical and laboratory features of primary antiphospholipid syndrome (PAPS) and that of secondary (SAPS) to systemic lupus erythematosus (SLE). METHODS: Twenty-seven PAPS and 32 SAPS patients were investigated in relation to the presence of arterial/venous thrombosis, fetal loss, reticular livedo, Raynaud phenomenon, autoimmune hemolytic anemia, thrombocytopenia, lymphopenia, anticardiolipin antibodies, lupus anticoagulant, antinuclear antibodies, anti-Sm and VDRL. Autoantibodies were investigated by ELISA (anticardiolipin and anti-Sm), indirect immunofluorescency (antinuclear antibodies) and by dilute prothrombin test, coagulation Kaolin test and dilute Russell viper venom test (lupus anticoagulant). RESULTS: Arterial thrombosis frequency was increased in PAPS (59.3% vs 25.0%, p=0.009) and venous thrombosis in SAPS (53.1% vs 33.3%; p>0.05), while there was no differences between frequencies of fetal loss (50.0% vs 56.7%), Raynaud phenomenon (18.5% vs 18.8%), reticular livedo (18.5% vs 12.5%), lupus anticoagulant (33.3% vs 37.5%), IgG anticardiolipin antibodies (79.2% vs 72,4%) and IgM anticardiolipin antibodies (58.4% vs 65.5%) in the two groups evaluated. Moreover, an increased frequency of lymphopenia (71.2% vs 7.4%; p<0.0001), antinuclear antibodies (100% vs 7.4%; p<0.0001) and positive VDRL (47.1% vs 5.0%, p=0.005) was observed in SAPS. CONCLUSIONS: Clinical and laboratory features were similar on PAPS and SAPS, although arterial thrombosis was associated to PAPS, and lymphopenia, antinuclear antibodies and VDRL were associated to SAPS.

Dois pacientes HIV-soronegativos com doença criptocócica refratária à terapia antifúngica convencional foram submetidos a estudo do sistema imune. Hipogamaglobulinemia foi evidenciada em ambos e associada à alteração funcional da imunidade mediada por células. Hipogamaglobulinemia é considerada como um possível fator predisponente para infecção criptocócica. A importância dos anticorpos no controle da infecção por Cryptococcus neoformans é discutida.

Two HIV-seronegative patients with cryptococcal disease refractory to conventional antifungal therapy were submitted to an evaluation of the immune system. Hypogammaglobulinemia was found in both and associated with abnormal function of cell-mediated immunity. Hypogammaglobulinemia is considered as a possible predisposing factor for cryptococcal infection. The importance of the antibodies on the control of Cryptococcus neoformans infection is discussed.