HLA Alleles in a Behçet Disease Multiethnic Population With and Without Ophthalmic Manifestations.

OBJECTIVE: The aim of this study was to analyze HLA alleles in patients with Behçet disease (BD) and their correlation with ophthalmic manifestations (OMs) in a multiethnic Brazilian population. METHODS: This case-control study compared 72 BD patients with or without OM who underwent a thorough ophthalmologic evaluation, including best-corrected visual acuity, bino-ophthalmoscopy, and HLA analysis, with 144 matched healthy controls. Fluorescein angiography was also performed in the patients with BD and OM. HLA class I (A, B, and C) and II (DRB1, DQB1, and DQA1) typing were performed using PCR-SSO. RESULTS: Of 72 patients with BD, 42 (58%) had OM. The HLA-B*51 and -A*26 alleles were more frequent in patients with BD than in controls (23.6% vs 14.6% and 12.5% vs 4.3%, respectively), but could not differentiate OM risk. The HLA alleles of BD patients that differentiated those with and without OM were HLA-B*15 (40.5% vs 20.7%; odds ratio [OR], 2.59; p = 0.0059), HLA-C*02 (33.3% vs 13.4%; OR, 3.20; p = 0.0024), and HLA-DQB1*03 (64.3% vs 45.7%, p = 0.017), whereas HLA-A*03 (0.0% vs 13.3%, p = 0.006) and HLA-DRB1*15 (4.8% vs 19.5%; OR, 0.21; p = 0.0121) were protective against OM. CONCLUSIONS: In this study of a Brazilian multiethnic BD population, alleles were similar between groups of BD patients with and without OM. We described HLA-B*15, -C*02, and -DQB1*03 as risk factors and -A*03 and -DRB1*15 as protective factors for OM in BD, which could function as biomarkers for predicting disease phenotypes.

Evaluation of endothelial function in patients with Behçet's disease in remission: A cross-sectional study.

OBJECTIVE: Endothelial dysfunction is an initial stage of the atherogenic process, which can be evaluated by a noninvasive method (flow-mediated dilation - FMD) and has a well-established prognostic value for cardiovascular (CV) risk. Currently, there is no evidence of increased CV mortality in Behc¸et's disease (BD), although its association with endothelial dysfunction has been described. There are still doubts in the literature whether the presence of chronic vascular inflammation might trigger the development of atherosclerosis, despite BD remission, which is why this study was conducted. METHODS: We analyzed 24 subjects in this cross-sectional study (12 patients with BD in remission and 12 subjects matched by gender age). Endothelial function was analyzed via FMD. RESULTS: The lowest median for FMD was presented by the BD group (2.025% - interquartile range (IQR) 7.785 versus 5.46% - IQR 3.625, P » .18). The median total cholesterol in the BD group was lower than the controls (168 mg dL-1 - IQR 46 and 216.5 mg dL-1 - IQR 54, respectively, P » .0193). In the right carotid artery, the intima-media thickness was equal to 0.740 - IQR 0.16 for the patients and 0.740 - IQR 0.11 for the controls (P » .9473); on the left, 0.725 - IQR 0.13 and 0.745 - IQR 0.120 (P » .4333), respectively. CONCLUSION: The lower median trend of FMD in patients with BD suggests endothelial dysfunction, despite clinical remission of the inflammatory disease, although our study is limited by the sample size and greater use of statins in BD group.

Incidence and risk factors for moderate/severe COVID-19 in rheumatic diseases patients on hydroxychloroquine: a 24-week prospective cohort.

OBJECTIVES: To evaluate the incidence of COVID-19 and its main outcomes in rheumatic disease (RD) patients on hydroxychloroquine (HCQ) compared to household cohabitants (HC). METHODS: This is a 24-week nationwide prospective multi-centre cohort with a control group without RD and not using HCQ. All participants were monitored through scheduled phone interviews performed by health professionals. Details regarding COVID-19 symptoms, and epidemiological, clinical, and demographic data were recorded on a specific web-based platform. COVID-19 was defined according to the Brazilian Ministry of Health criteria and classified as mild, moderate or severe. RESULTS: A total of 9,585 participants, 5,164 (53.9%) RD patients on HCQ and 4,421 (46.1%) HC were enrolled from March 29th, 2020 to September 30th, 2020, according to the eligibility criteria. COVID-19 confirmed cases were higher in RD patients than in cohabitants [728 (14.1%) vs. 427 (9.7%), p<0.001] in a 24-week follow-up. However, there was no significant difference regarding outcomes related to moderate/ severe COVID-19 (7.1% and 7.3%, respectively, p=0.896). After multiple adjustments, risk factors associated with hospitalisation were age over 65 (HR=4.5; 95%CI 1.35-15.04, p=0.014) and cardiopathy (HR=2.57; 95%CI 1.12-5.91, p=0.026). The final survival analysis demonstrated the probability of dying in 180 days after a COVID-19 diagnosis was significantly higher in patients over 65 years (HR=20.8; 95%CI 4.5-96.1) and with 2 or more comorbidities (HR=10.8; 95%CI 1.1-107.9 and HR=24.8; 95%CI 2.5-249.3, p=0.006, respectively). CONCLUSIONS: Although RD patients have had a higher COVID-19 incidence than individuals from the same epidemiological background, the COVID-19 severity was related to traditional risk factors, particularly multiple comorbidities and age, and not to underlying RD and HCQ.

Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil.

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).

Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil

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).

Epidemiologic Features of Systemic Vasculitides in the Southeast Region of Brazil: Hospital-Based Survey.

BACKGROUND/OBJECTIVE: The epidemiology of vasculitis is variable in different geographic areas, and this issue has not been approached in Brazil yet. The objective of this study was to assess the frequency of vasculitis in specialized centers in Brazil. METHODS: This cross-sectional study was performed in 9 vasculitis outpatient clinics from 6 different states mainly from the Southeast and the Northeast regions of Brazil between 2015 and 2017. Diagnosis and/or classification criteria for Behçet disease (BD), Takayasu arteritis (TA), giant cell arteritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and cryoglobulinemic vasculitis (CryoVas) were used to include patients with at least 6 months of follow-up in this hospital-based survey. RESULTS: A total of 1233 patients with systemic vasculitis were included from the Southeast region. Behçet disease was the most frequent vasculitis (35.0%) followed by TA (26.4%), GPA (16.2%), PAN (5.8%), GCA (5.8%), EGPA (4.3%), MPA (3.4%), and CryoVas (3.0%). Up to 7.8% of vasculitis patients had a juvenile onset, and the frequency of vasculitides found in children and adolescents was as follows: TA (52.6%), BD (24.7%), GPA (12.4%), and PAN (10.3%). No cases of EGPA, MPA, and CryoVas were diagnosed before the age of 18 years. As a comparator, 103 vasculitis patients were included in the Northeast of Brazil where TA was found in 36.9% and BD in 31.1% of vasculitis cases. No GCA cases were found in the Northeast part of Brazil. CONCLUSIONS: Similar to the epidemiology of vasculitis in Asia, BD and TA are the most frequent vasculitis in Southeastern Brazilian referral centers.

Recommendations of the Brazilian Society of Rheumatology for the induction therapy of ANCA-associated vasculitis.

The purpose of these recommendations is to guide the appropriate induction treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with active disease. The recommendations proposed by the Vasculopathies Committee of the Brazilian Society Rheumatology for induction therapy of AAV, including granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis, were based on systematic literature review and expert opinion. Literature review was performed using Medline (PubMed), EMBASE and Cochrane database to retrieve articles until October 2016. PRISMA guidelines were used for the systematic review and articles were assessed according to the Oxford levels of evidence. Sixteen recommendations were made regarding different aspects of induction therapy for AAV. The purpose of these recommendations is to serve as a guide for therapeutic decisions by health care professionals in the management of AAV patients presenting active disease.

Interleukin 6 Inhibition and Coronary Artery Disease in a High-Risk Population: A Prospective Community-Based Clinical Study.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease, with interleukin 6 (IL-6) as a major player in inflammation cascade. IL-6 blockade may reduce cardiovascular risk, but current treatments to block IL-6 also induce dyslipidemia, a finding with an uncertain prognosis. METHODS AND RESULTS: We aimed to determine the endothelial function responses to the IL-6-blocking agent tocilizumab, anti-tumor necrosis factor α, and synthetic disease-modifying antirheumatic drug therapies in patients with rheumatoid arthritis in a 16-week prospective study. Sixty consecutive patients with rheumatoid arthritis were enrolled. Tocilizumab and anti-tumor necrosis factor α therapy were started in 18 patients each while 24 patients were treated with synthetic disease-modifying antirheumatic drugs. Forty patients completed the 16-week follow-up period. The main outcome was flow-mediated dilation percentage variation before and after therapy. In the tocilizumab group, flow-mediated dilation percentage variation increased statistically significantly from a pre-treatment mean of (3.43% [95% CI, 1.28-5.58] to 5.96% [95% CI, 3.95-7.97]; P=0.03). Corresponding changes were 4.78% (95% CI, 2.13-7.42) to 6.75% (95% CI, 4.10-9.39) (P=0.09) and 2.87% (95% CI, -2.17 to 7.91) to 4.84% (95% CI, 2.61-7.07) (P=0.21) in the anti-tumor necrosis factor α and the synthetic disease-modifying antirheumatic drug groups, respectively (both not statistically significant). Total cholesterol increased significantly in the tocilizumab group from 197.5 (95% CI, 177.59-217.36) to 232.3 (201.62-263.09) (P=0.003) and in the synthetic disease-modifying antirheumatic drug group from 185.8 (95% CI, 169.76-201.81) to 202.8 (95% CI, 176.81-228.76) (P=0.04), but not in the anti-tumor necrosis factor α group. High-density lipoprotein did not change significantly in any group. CONCLUSIONS: Endothelial function is improved by tocilizumab in a high-risk population, even as it increases total cholesterol and low-density lipoprotein levels.

Ocular involvement in patients with spondyloarthritis.

Ocular inflammatory diseases can present as isolated conditions but also as part of systemic inflammatory diseases. Anterior uveitis is closely related to SpA and shares the common genetic background of HLA-B27. Other ocular manifestations, such as episcleritis and scleritis, may also occur, although less frequently. Therefore, ocular involvement has been included as one of the important clinical features of SpA in the recently published classification criteria for axial and peripheral disease. However, there are a wide variety of aetiologies for ocular diseases and this must be considered in assessment of SpA.

Recommendations of the Brazilian Society of Rheumatology for the induction therapy of ANCA-associated vasculitis / Recomendações da Sociedade Brasileira de Reumatologia para a terapia de indução para vasculite associada a ANCA

Abstract The purpose of these recommendations is to guide the appropriate induction treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with active disease. The recommendations proposed by the Vasculopathies Committee of the Brazilian Society Rheumatology for induction therapy of AAV, including granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis, were based on systematic literature review and expert opinion. Literature review was performed using Medline (PubMed), EMBASE and Cochrane database to retrieve articles until October 2016. PRISMA guidelines were used for the systematic review and articles were assessed according to the Oxford levels of evidence. Sixteen recommendations were made regarding different aspects of induction therapy for AAV. The purpose of these recommendations is to serve as a guide for therapeutic decisions by health care professionals in the management of AAV patients presenting active disease.

Resumo O objetivo destas recomendações é orientar o tratamento apropriado de indução em pacientes com vasculite associada a anticorpos anticitoplasma de neutrófilos (VAA) ativa. As recomendações propostas pelo Comitê de Vasculopatias da Sociedade Brasileira de Reumatologia para a terapia de indução para vasculites associadas aos anticorpos anticitoplasma de neutrófilos (VAA), inclusive granulomatose com poliangiite, poliangiite microscópica e vasculite limitada ao rim, foram baseadas em uma revisão sistemática da literatura e na opinião de especialistas. A revisão da literatura foi feita com as bases de dados Medline (PubMed), Embase e Cochrane para consultar artigos até outubro de 2016. As diretrizes Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Principais itens para reportar revisões sistemáticas e metanálises) foram usadas para a revisão sistemática e os artigos foram avaliados de acordo com os níveis de evidência Oxford. Dezesseis recomendações foram feitas em relação a diferentes aspectos da terapia de indução para VAA. O objetivo dessas recomendações é servir como um guia para decisões terapêuticas por profissionais da saúde no tratamento de pacientes com VAA que apresentem a doença ativa.

Abordagem terapêutica das vasculites pulmonares / Therapeutic approach to pulmonary vasculitis

Muitas vasculites sistêmicas acometem o trato respiratório. O acometimento mais frequente é o do parênquima pulmonar pelas vasculites de pequenos vasos ANCA associadas (antineutrophil cytoplasmic antibodies), que incluem a granulomatose com poliangite (GPA, antiga granulomatose de Wegener), a poliangite microscópica (MPA), granulomatose eosinofílica com poliangite (EGPA, antiga doença de Churg-Strauss). Este artigo propõe-se a revisar o tratamento dessas doenças de acordo com recomendações da liga europeia de combate ao reumatismo (EULAR), com base no estádio e na atividade de doença, incluindo as terapia usadas na indução e na manutenção de remissão, assim como nos casos refratários ao tratamento convencional

There are many vasculitis that affect the respiratory tract. The pulmonary parenchyma is the most frequently involved and occurs mainly in ANCA associated small vessel vasculitis (antineutrophil cytoplasmic antibodies), which include granulomatosis with polyangitis (GPA, formely Wegener's granulomatosis), microscopic polyangitis (MPA), eosinophilic granulomatosis with polyangitis (EGPA formely Churg-Strauss Syndrome). This article reviews the treatment of them, according to EULAR (European League Against Rheumatism) recommendations, which are based on stage and severity of disease, including induction and maintance therapy, and therapy of refractory disease

Classificação e clínica das vasculites pulmonares / Clinical classification of pulmonary vasculitis

As vasculites sistêmicas são doenças raras e heterogêneas que acometem diferentes sistemas. A gravidade da manifestação clínica depende do tamanho, local e extensão do comprometimento do leito vascular. O reconhecimento das manifestações clínicas por diferentes especialidades médicas permite o diagnóstico e o tratamento precoce, interferindo decisivamente no prognóstico. Muitas dessas doenças acometem o trato respiratório e o pneumologista é, com frequência, o especialista envolvido na propedêutica inicial. É importante conhecer as formas de classificação desenvolvidas na tentativa de categorizar as vasculites. O presente artigo propõe-se a rever tais classificações, assim como as doenças que acometem o trato respiratório e os possíveis diagnósticos diferenciais que costuam mimetizar as vasculites. Destacamos que o acometimento pulmonar ocorre principalmente nas vasculites de pequenos vasos, associados ao ANCA (antineutrophil cytoplasmic antibodies), que incluem a granulomatose com poliangite (GPA, antiga granulomatose de Wegener), a poliangite microscópica (MPA), granulomatose eosinofílica com poliangite (EGPA, antiga doença de Churg-Strauss). A respeito dos critérios classificatórios do American College of Rheumatology (ACR), reforçamos que servem para nomear e classificar a vasculite previamente documentada, mas não incluem o exame de ANCA e apresentam restrições em separar pacientes com GPA e MPA

Systemic vasculitis are rare and heterogenous diseases that affect different systems. The severity of clinical manifestation depends on the size, location and distribution of vessel involvement. The prompt recognition of the clinical manifestations allows early diagnosis and treatment, improving the prognosis. There are many vasculitis that affect the respiratory tract, therefore the pulmonologist is often a specialist involved in the initial workup. It is important to know the forms of classification developed in an attempt to categorize vasculitis. This article proposes to revise such classification, as well as diseases affecting the respiratory tract and the possible diferential diagnoses that often mimic vasculitis. We emphasize that the pulmonary involvement occurs mainly in ANCA-associated smal vessel vasculitis (antineutrophil cytoplasmic antibodies), which include granumatosis with polyangitis (GPA, formely Wegener's granulomatosis), microscopic polyangitis (MPA), eosinophilic granulomatosis with polyangitis (EGPA formely Churg-Strauss Syndrome). Regarding the classification criteria of the American College of Rheumatology (ACR), it is important to reinforce its use in naming and classifying vasculitis after rule out infectious and neoplasic diseases, but remember that it does not include the ANCA exam and has its limits in separating patients with GPA and MPA A

Giant cell arteritis: a multicenter observational study in Brazil.

OBJECTIVE: To describe demographic features, disease manifestations and therapy in patients with giant cell arteritis from referral centers in Brazil. METHODS: A retrospective cohort study was performed on 45 giant cell arteritis patients from three university hospitals in Brazil. Diagnoses were based on the American College of Rheumatology classification criteria for giant cell arteritis or temporal artery biopsy findings. RESULTS: Most patients were Caucasian, and females were slightly more predominant. The frequencies of disease manifestations were as follows: temporal headache in 82.2%, neuro-ophthalmologic manifestations in 68.9%, jaw claudication in 48.9%, systemic symptoms in 44.4%, polymyalgia rheumatica in 35.6% and extra-cranial vessel involvement in 17.8% of cases. Aortic aneurysms were observed in 6.6% of patients. A comparison between patients with biopsy-proven giant cell arteritis and those without temporal artery biopsies did not yield significant differences in disease manifestations. All patients were treated with oral prednisone, and intravenous methylprednisolone was administered to nearly half of the patients. Methotrexate was the most commonly used immunosuppressive agent, and low-dose aspirin was prescribed to the majority of patients. Relapses occurred in 28.9% of patients, and aspirin had a protective effect against relapses. Females had higher prevalences of polymyalgia rheumatica, systemic manifestations and jaw claudication, while permanent visual loss was more prevalent in men. CONCLUSIONS: Most of the clinical features of Brazilian giant cell arteritis patients were similar to those found in other studies, except for the high prevalence of neuro-ophthalmic manifestations and permanent blindness in the Brazilian patients. Aspirin had a protective effect on relapses.

Giant cell arteritis: a multicenter observational study in Brazil

OBJECTIVE: To describe demographic features, disease manifestations and therapy in patients with giant cell arteritis from referral centers in Brazil. METHODS: A retrospective cohort study was performed on 45 giant cell arteritis patients from three university hospitals in Brazil. Diagnoses were based on the American College of Rheumatology classification criteria for giant cell arteritis or temporal artery biopsy findings. RESULTS: Most patients were Caucasian, and females were slightly more predominant. The frequencies of disease manifestations were as follows: temporal headache in 82.2%, neuro-ophthalmologic manifestations in 68.9%, jaw claudication in 48.9%, systemic symptoms in 44.4%, polymyalgia rheumatica in 35.6% and extra-cranial vessel involvement in 17.8% of cases. Aortic aneurysms were observed in 6.6% of patients. A comparison between patients with biopsy-proven giant cell arteritis and those without temporal artery biopsies did not yield significant differences in disease manifestations. All patients were treated with oral prednisone, and intravenous methylprednisolone was administered to nearly half of the patients. Methotrexate was the most commonly used immunosuppressive agent, and low-dose aspirin was prescribed to the majority of patients. Relapses occurred in 28.9% of patients, and aspirin had a protective effect against relapses. Females had higher prevalences of polymyalgia rheumatica, systemic manifestations and jaw claudication, while permanent visual loss was more prevalent in men. CONCLUSIONS: Most of the clinical features of Brazilian giant cell arteritis patients were similar to those found in other studies, except for the high prevalence of neuro-ophthalmic manifestations and permanent blindness in the Brazilian patients. Aspirin had a protective effect on relapses.