Abstract Immunoglobulin G4-related disease is a systemic immune-mediated disease with insidious evolution characterized by fibroinflammatory lesions over virtually any organ system. Despite the remarkable progression of knowledge, its etiology remains undefined. Due to its relapse-remitting pattern, it could accumulate irreversible damage, increasing comorbidities and mortality. This paper emphasizes key concepts for diagnosing and treating patients with this condition. G4related Grelated G4 related G immunemediated immune mediated system knowledge undefined relapseremitting relapse remitting pattern damage mortality condition

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

Abstract 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 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.

Resumo Objetivo: Avaliar os parâmetros associados à qualidade de vida em pacientes com doença de Paget óssea (DPO). Métodos: Avaliaram-se pacientes com DPO com os questionários SF-36 e WHOQOL-bref. Excluíram-se pacientes com outras doenças que pudessem causar comprometimento significativo da qualidade de vida. Buscou-se por correlações entre os resultados e idade, tempo de diagnóstico, tipo de envolvimento, dor relacionada com a DPO, limitação às atividades diárias, deformidades, fosfatase alcalina específica do osso, extensão do envolvimento e tratamento. Resultados: Incluíram-se 50 pacientes. Os resultados da pontuação total do SF-36 e seus domínios, saúde física e saúde mental, se correlacionaram significativamente com a dor óssea e deformidades. O estado civil se correlacionou significativamente com a pontuação total do SF-36 e com seu domínio saúde mental. Os níveis de BAP e a extensão da doença se correlacionaram significativamente com o domínio saúde física do SF-36. Depois da análise multivariada, os únicos parâmetros que permaneceram significativamente associados à pontuação total do SF-36 e aos seus domínios saúde mental e saúde física foram a dor e o estado civil. A pontuação total do WHOQOL-bref esteve significativamente associada à dor, ao comprometimento físico e a deformidades. O escore do Domínio 1 (físico) do WHOQOL-bref esteve significativamente associado ao estado civil, dor e deformidades, enquanto o Domínio 2 (psicológico) esteve associado ao estado civil, comprometimento físico e tipo de envolvimento. Depois da análise multivariada, a presença de dor, deformidades e estado civil esteve significativamente associada à pontuação total do WHOQOL-bref e à pontuação do seu Domínio 1. Os resultados do WHOQOL-bref 2 foram significativamente preditos pela dor e pelo estado civil. Conclusão: O principal fator associado aos escores do SF-36 foi a dor óssea, enquanto a dor óssea e as deformidades estiveram associadas ao WHOQOL-bref.

Abstract Objective: To evaluate the parameters associated with quality of life in patients with Paget's disease of bone. Methods: Patients with Paget's disease of bone were evaluated with SF-36 and WHOQOL-bref questionnaires. Patients with other diseases that could cause significant impairment of their quality of life were excluded. We searched for correlations between the results and: age, time from diagnosis, type of involvement, pain related to Paget's disease of bone, limitation to daily activities, deformities, bone specific alkaline phosphatase, the extent of involvement and treatment. Results: Fifty patients were included. Results of the SF-36 total score and its domains, physical and mental health, were significantly correlated with bone pain and deformities. Marital status was significantly correlated with the SF-36 total score and Mental Health Domain. BAP levels and disease extension were significantly correlated to SF-36 Physical Health Domain. After multivariate analysis, the only parameters that remained significantly associated with the SF-36 total score and to its Mental Health and Physical Health Domains were pain and marital status.The WHOQOL-bref total score was significantly associated with pain, physical impairment and deformities. WHOQOL-bref Domain 1 (physical) score was significantly associated with marital status, pain and deformities, while Domain 2 (psychological) score was associated with marital status, physical impairment and kind of involvement. After multivariate analysis, the presence of pain, deformities, and marital status were significantly associated with results of the WHOQOL-bref total score and its Domain 1. WHOQOL-bref domain 2 results were significantly predicted by pain and marital status. Conclusion: The main disease-related factor associated with SF-36 results in Paget's disease of bone patients was bone pain, while bone pain and deformities were associated with WHOQOL-bref.

Resumo Em 2014, o tofacitinibe, um medicamento modificador do curso da doença (MMCD) sintético, alvo-específico, inibidor seletivo das Janus quinases (JAK), foi aprovado para uso no Brasil. Este documento de posicionamento tem o objetivo de atualizar as recomendações da Sociedade Brasileira de Reumatologia (SBR) sobre o tratamento da artrite reumatoide (AR) no Brasil, especificamente com relação ao uso de MMCD sintéticos alvo-específicos. O método dessa recomendação incluiu revisão bibliográfica de artigos científicos, feita na base de dados Medline. Após a revisão, foi produzido um texto, que responde a perguntas na estrutura Pico, e considera questões de eficácia e segurança do uso do tofacitinibe para tratamento de AR em diferentes situações (como primeira linha de tratamento, após falha ao metotrexato [MTX] ou outros MMCD sintéticos convencionais, após falha da terapia biológica). Com base nas evidências existentes, e considerando os dados disponíveis sobre eficácia, segurança e custo das medicações disponíveis para tratamento da doença no Brasil, a Comissão de AR da SBR, após processo de discussão e votação de propostas, estabeleceu o seguinte posicionamento sobre o uso de tofacitinibe para o tratamento da AR no Brasil: “Tofacitinibe, em monoterapia ou em associação ao MTX, é uma opção para os pacientes com AR em atividade moderada ou alta, após falha de pelo menos dois esquemas com diferentes MMCD sintéticos e um esquema de MMCD biológico”. O grau de concordância com essa recomendação foi 7,5. Esse posicionamento poderá ser revisto nos próximos anos, com a maior experiência adquirida com o uso do medicamento.

Abstract In 2014, tofacitinib, a target-specific, synthetic disease modifying anti rheumatic drug (DMARD) and a selective inhibitor of Janus kinase (JAK) was approved for use in Brazil. This position paper aims to update the recommendations of the Brazilian Society of Rheumatology (SBR) on the treatment of rheumatoid arthritis (RA) in Brazil, specifically regarding the use of target-specific synthetic DMARDs. The method of this recommendation consisted of a literature review of scientific papers held on the Medline database. After this review, a text was produced, answering questions in Pico structure, considering efficacy and safety issues of tofacitinib use for RA treatment in different scenarios (such as first-line treatment after failure with methotrexate [MTX] or other conventional synthetic DMARDs after failure with biological therapy). Based on existing evidence, and considering the available data on efficacy, safety and cost of medications available to treat the disease in Brazil, the RA Commission of SBR, after a process of discussion and voting on proposals, established the following position on the use of tofacitinib for treatment of RA in Brazil: “Tofacitinib, alone or in combination with MTX, is an alternative for RA patients with moderate or high activity after failure of at least two different synthetic DMARDs and one biological DMARD.” The level of agreement with this recommendation was 7.5. This position may be reviewed in the coming years, in the face of a greater experience with the use of this medication.

INTRODUÇÃO: Embora muitos estudos sugiram que a presença de autoanticorpos, tais como fator reumatoide (FR) e/ou antipeptídeos citrulinados cíclicos (anti-CCP), sejam preditores de danos articulares na artrite reumatoide (AR), a associação entre os questionários de incapacidade e de qualidade de vida ainda são desconhecidos. OBJETIVOS: Avaliar a correlação entre os questionários Health Assessment Questionnaire (HAQ) e Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) com marcadores como FR, anti-CCP e antivimentina citrulinada (anti-Sa). PACIENTES E MÉTODOS: Foram avaliados no momento do diagnóstico 65 pacientes da Coorte Brasília com AR inicial. Foram realizadas sorologias (ELISA) para FR (IgM, IgG e IgA), anti-CCP (CCP2, CCP3 e CCP3.1) e anti-Sa, com a aplicação do HAQ e SF-36 na avaliação inicial. RESULTADOS: A idade média foi de 45 anos, predominando o gênero feminino (86%). Na avaliação inicial, o FR foi positivo em 32 indivíduos (49,23%); anti-CCP em 34 indivíduos (52,3%); e anti-Sa em nove indivíduos (13,8%). O escore inicial do HAQ foi de 1,8. Os escores dos domínios do SF-36 foram: emocional, 19,3; social, 43,1; dor, 25,43; estado geral, 57,6; saúde mental, 48,1; vitalidade, 49,5; físico, 4,6; e limitação por aspecto físico, 24,7. HAQ e escores do SF-36 não variaram com os níveis de autoanticorpos. CONCLUSÃO: Muitos pacientes com AR inicial apresentam comprometimento na qualidade de vida relacionada aos domínios da capacidade física e mental. Embora FR e anti-CCP tenham sido relacionados com dano articular e pior prognóstico clínico, não há correlação entre os questionários e as avaliações da qualidade de vida e incapacidade.

INTRODUCTION: Although many studies have suggested that the presence of autoantibodies, such as rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) in rheumatoid arthritis (RA) are predictors of joint damage, the association with disability and quality of life questionnaires are not known. OBJECTIVES: To evaluate the correlation between the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) scores with serological markers, such as RF, anti-CCP, and anti-citrullinated vimentin (anti-Sa). PATIENTS AND METHODS: Sixty five patients with early RA (ERA) from the Brasília Cohort of ERA were evaluated. Serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1), and anti-Sa were performed, with the application of the HAQ and SF-36 questionnaires in the initial evaluation. RESULTS: The mean age was 45 years, with a female predominance (86%). At the initial evaluation, RF was positive in 32 individuals (49.23%), anti-CCP in 34 (52.3%), and anti-Sa in nine (13.8%). The initial HAQ score was 1.8. The SF-36 scores were as follow: role-emotional, 19.3; social functioning, 43.1; bodily pain, 25.43; general health, 57.6; mental health, 48.1; vitality, 49.5; role-physical, 4.6; and physical functioning, 24.7. The HAQ and SF-36 scores did not vary with autoantibody levels. CONCLUSION: In many patients, ERA has a major impact on physical ability and health-related quality of life. Although RF and anti-CCP tests have been related with joint destruction and worse clinical prognosis, there is no correlation with the results of questionnaires of quality of life and disability.

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: Elaborar recomendações para o manejo da artrite reumatoide (AR) no Brasil, com enfoque no diagnóstico e na avaliação inicial da doença. MÉTODO: Revisão da literatura e opinião de especialistas membros da Comissão de AR da Sociedade Brasileira de Reumatologia. RESULTADOS E CONCLUSÕES: Foram estabelecidas 10 recomendações: 1) O diagnóstico da AR deve ser estabelecido considerando-se achados clínicos e exames complementares; 2) Deve-se dedicar especial atenção ao diagnóstico diferencial dos casos de artrite; 3) O fator reumatoide (FR) é um teste diagnóstico importante, porém com sensibilidade e especificidade limitadas, sobretudo na AR inicial; 4) O anti-CCP (teste para anticorpos antipeptídeos citrulinados cíclicos) é um marcador com sensibilidade semelhante a do FR, mas com especificidade superior, sobretudo na fase inicial da doença; 5) Embora inespecíficas, provas de atividade inflamatória devem ser solicitadas a pacientes com suspeita clínica de AR; 6) A radiografia convencional deve ser empregada para avaliação de diagnóstico e prognóstico da doença. Quando necessário e disponível, a ultrassonografia e a ressonância magnética podem ser utilizadas; 7) Podem-se utilizar critérios de classificação de AR (ACR/EULAR 2010), embora ainda não validados, como um guia para auxiliar no diagnóstico de pacientes com artrite inicial; 8) Deve-se utilizar um dos índices compostos para avaliação de atividade de doença; 9) Recomenda-se a utilização regular de ao menos um instrumento de avaliação da capacidade funcional; 10) Deve-se verificar, na avaliação inicial da doença, a presença ou não de fatores de pior prognóstico, como o acometimento poliarticular, FR e/ou anti-CCP em títulos elevados e erosão articular precoce.

OBJECTIVE: Develop guidelines for management of rheumatoid arthritis (RA) in Brazil, focusing on diagnosis and early assessment of the disease. METHOD: Literature review and expert opinions of RA Committee members of the Brazilian Society of Rheumatology. RESULTS AND CONCLUSIONS: The following ten reccommendations were established: 1) RA diagnosis should be established considering clinical findings and complementary test results; 2) Special attention should be given to the differential diagnosis of arthritis; 3) Rheumatoid factor (RF) is an important diagnostic test, but has limited sensitivity and specificity, mainly in early RA; 4) Anti-CCP (anti-cyclic citrullinated peptide antibody) is a marker with sensitivity similar to that of the RF, but with higher specificity, mainly in the initial phase of disease; 5) Although unspecific, acute-phase reactants should be measured in patients with clinical suspicion of RA; 6) Conventional radiography should be performed for diagnostic and prognostic assessment of the disease. When necessary and available, ultrasound and magnetic resonance may be used; 7) Rheumatoid arthritis classification criteria (ACR/EULAR 2010), although not yet validated, may be used as a guide to aid in diagnosing patients with early RA; 8) One of the combined disease activity indices should be used to assess disease activity; 9) At least one of the functional capacity assessment instruments, such as mHAQ or HAQ-DI, should be regularly used; 10) At the early assessment of the disease, the presence of worse prognostic factors, such as polyarticular involvement, high titers of RF and/or anti-CCP, and early joint erosion, should be investigated.