Uncovering the knowledge about systemic amyloidosis relevant to the rheumatologists.

Amyloidosis is a localized or systemic disease caused by deposition of proteins in the extracellular space of various organs and tissues. As part of the disease, proteins that were originally soluble misfold and acquire a fibrillar conformation that renders them insoluble and resistant to proteolysis. Systemic amyloidosis is a rare, often underdiagnosed condition. In recent years, the incidence of newly diagnosed cases of amyloidosis has been increasing in association with the aging of the population and greater access to diagnostic tests. From a clinical perspective, systemic amyloidosis is frequently associated with involvement of the kidneys (causing nephrotic syndrome), heart (cardiac failure and arrhythmia), and peripheral nervous system (sensorimotor polyneuropathy and autonomic dysfunction). This condition is important to the rheumatologist for several reasons, such as its systemic involvement that mimics autoimmune rheumatic diseases, its musculoskeletal manifestations, which when recognized can allow the diagnosis of amyloidosis, and also because reactive or secondary AA amyloidosis is a complication of rheumatic inflammatory diseases. The treatment of amyloidosis depends on the type of amyloid protein involved. Early recognition of this rare disease is fundamental for improved clinical outcomes.

Rare diseases: What rheumatologists need to know?

Although the terms "rare diseases" (RD) and "orphan diseases" (OD) are often used interchangeably, specific nuances in definitions should be noted to avoid misconception. RD are characterized by a low prevalence within the population, whereas OD are those inadequately recognized or even neglected by the medical community and drug companies. Despite their rarity, as our ability on discovering novel clinical phenotypes and improving diagnostic tools expand, RD will continue posing a real challenge for rheumatologists. Over the last decade, there has been a growing interest on elucidating mechanisms of rare autoimmune and autoinflammatory rheumatic diseases, allowing a better understanding of the role played by immune dysregulation on granulomatous, histiocytic, and hypereosinophilic disorders, just to name a few. This initiative enabled the rise of innovative targeted therapies for rheumatic RD. In this review, we explore the state-of-the art of rare RD and the critical role played by rheumatologists in healthcare. We also describe the challenges rheumatologists may face in the coming decades.

[Psoriasis induced by a TNF-alpha antagonist in a patient with ulcerative colitis]. / Psoríase induzida por antagonista de TNF-alfa em paciente com retocolite ulcerativa inespecifica.

Infliximab is an anti-TNF alpha and it has been used to treat ulcerative colitis refractory to other treatments since 2006, which is associated to quick induction and sustained remission of disease, as well as improvement of health related-quality of life. The most frequent adverse effects are formation of antibodies against anti-TNF alpha, acute allergic reactions, hypersensitivity reactions, lymphoproliferative diseases, susceptibility to infections, reactivation of latent extrapulmonary tuberculosis. We describe a case of psoriasis induced by anti-TNF, rarely described in literature. So we conducted a review on the mechanisms involved in this process, since this drug is also used in primary treatment of psoriasis.

DNMT3B (rs2424913) polymorphism is associated with systemic lupus erythematosus alone and with co-existing periodontitis in a Brazilian population.

The association between Periodontitis and Systemic Lupus Erythematosus (SLE) has been primarily based on their similar pathophysiology and both are associated with genetic polymorphisms. OBJECTIVES: To investigate an association between the methylation-related gene polymorphisms DNMT3B (rs2424913) and MTHFR (rs1801133) to Systemic Lupus Erythematosus (SLE) and Periodontitis. METHODOLOGY: In total, 196 individuals of all genders aged 24 to 60 years old were allocated into four groups based on their systemic and periodontal status, namely: Healthy control (n=60), periodontitis (n=51), SLE (n=47), and SLE + periodontitis (n=38). Individuals with SLE were stratified according to disease activity (SLEDAI) in inactive or active. We performed polymorphism analysis using PCR-RFLP with genomic DNA from mouthwash. We analyzed data using Fisher's Exact, Chi-square test, and regression models. RESULTS: Periodontal status were similar in subjects with periodontitis alone and combined with SLE. SLE patients with periodontitis had a longer SLE diagnosis than SLE only (p=0.001). For DNMT3 B polymorphism, the periodontitis, SLE, and Inactive SLE + periodontitis groups showed a higher frequency of T allele and TT genotypes compared to healthy controls (p<0.05). Regression analyses showed that the TT genotype is a strong risk factor for periodontitis (OR=4.53; CI95%=1.13-18.05) and also for SLE without periodontitis (OR=11.57; CI95%=3.12-42.84) and SLE with periodontitis (OR=5.27; CI95%=1.25-22.11) when compared to control. CONCLUSION: SLE patients with periodontitis had a longer length of SLE diagnosis. The DNMT3B (rs2424913) polymorphism was associated with periodontitis and SLE alone or combined with periodontitis. Our study contributes to understanding the genetic mechanisms involved in periodontitis and SLE susceptibility.

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases.

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. 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.

DNMT3B (rs2424913) polymorphism is associated with systemic lupus erythematosus alone and with co-existing periodontitis in a Brazilian population

Abstract The association between Periodontitis and Systemic Lupus Erythematosus (SLE) has been primarily based on their similar pathophysiology and both are associated with genetic polymorphisms. Objectives: To investigate an association between the methylation-related gene polymorphisms DNMT3B (rs2424913) and MTHFR (rs1801133) to Systemic Lupus Erythematosus (SLE) and Periodontitis. Methodology: In total, 196 individuals of all genders aged 24 to 60 years old were allocated into four groups based on their systemic and periodontal status, namely: Healthy control (n=60), periodontitis (n=51), SLE (n=47), and SLE + periodontitis (n=38). Individuals with SLE were stratified according to disease activity (SLEDAI) in inactive or active. We performed polymorphism analysis using PCR-RFLP with genomic DNA from mouthwash. We analyzed data using Fisher's Exact, Chi-square test, and regression models. Results: Periodontal status were similar in subjects with periodontitis alone and combined with SLE. SLE patients with periodontitis had a longer SLE diagnosis than SLE only (p=0.001). For DNMT3 B polymorphism, the periodontitis, SLE, and Inactive SLE + periodontitis groups showed a higher frequency of T allele and TT genotypes compared to healthy controls (p<0.05). Regression analyses showed that the TT genotype is a strong risk factor for periodontitis (OR=4.53; CI95%=1.13-18.05) and also for SLE without periodontitis (OR=11.57; CI95%=3.12-42.84) and SLE with periodontitis (OR=5.27; CI95%=1.25-22.11) when compared to control. Conclusion: SLE patients with periodontitis had a longer length of SLE diagnosis. The DNMT3B (rs2424913) polymorphism was associated with periodontitis and SLE alone or combined with periodontitis. Our study contributes to understanding the genetic mechanisms involved in periodontitis and SLE susceptibility.

Recommendations of the Brazilian Society of Rheumatology for diagnosis and treatment of Chikungunya fever. Part 1 - Diagnosis and special situations.

Chikungunya fever has become a relevant public health problem in countries where epidemics occur. Until 2013, only imported cases occurred in the Americas, but in October of that year, the first cases were reported in Saint Marin island in the Caribbean. The first autochthonous cases were confirmed in Brazil in September 2014; until epidemiological week 37 of 2016, 236,287 probable cases of infection with Chikungunya virus had been registered, 116,523 of which had serological confirmation. Environmental changes caused by humans, disorderly urban growth and an ever-increasing number of international travelers were described as the factors responsible for the emergence of large-scale epidemics. Clinically characterized by fever and joint pain in the acute stage, approximately half of patients progress to the chronic stage (beyond 3 months), which is accompanied by persistent and disabling pain. The aim of the present study was to formulate recommendations for the diagnosis and treatment of Chikungunya fever in Brazil. A literature review was performed in the MEDLINE, SciELO and PubMed databases to ground the decisions for recommendations. The degree of concordance among experts was established through the Delphi method, involving 2 in-person meetings and several online voting rounds. In total, 25 recommendations were formulated and divided into 3 thematic groups: (1) clinical, laboratory and imaging diagnosis; (2) special situations; and (3) treatment. The first 2 themes are presented in part 1, and treatment is presented in part 2.

Recommendations of the Brazilian Society of Rheumatology for the diagnosis and treatment of chikungunya fever. Part 2 - Treatment.

Chikungunya fever has become an important public health problem in countries where epidemics occur because half of the cases progress to chronic, persistent and debilitating arthritis. Literature data on specific therapies at the various phases of arthropathy caused by chikungunya virus (CHIKV) infection are limited, lacking quality randomized trials assessing the efficacies of different therapies. There are a few studies on the treatment of musculoskeletal manifestations of chikungunya fever, but these studies have important methodological limitations. The data currently available preclude conclusions favorable or contrary to specific therapies, or an adequate comparison between the different drugs used. The objective of this study was to develop recommendations for the treatment of chikungunya fever in Brazil. A literature review was performed via evidence-based selection of articles in the databases Medline, SciELO, PubMed and Embase and conference proceedings abstracts, in addition to expert opinions to support decision-making in defining recommendations. The Delphi method was used to define the degrees of agreement in 2 face-to-face meetings and several online voting rounds. This study is part 2 of the Recommendations of the Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia - SBR) for the Diagnosis and Treatment of chikungunya fever and specifically addresses treatment.

IgA nephropathy in systemic lupus erythematosus patients: case report and literature review.

Systemic erythematosus lupus (SLE) is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non-lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN), the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1280, nuclear fine speckled pattern, and anticardiolipin IgM and 280U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non-SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in both the short and long terms.

Arterial occlusion in systemic lupus erythematosus: a good prognostic sign?

Arterial occlusion with subsequent amputation of extremities is a rare manifestation of systemic lupus erythematosus (SLE). It may be caused by local arteritis and/or thrombosis. We describe the clinical and laboratory manifestations and treatment administered to six SLE patients who developed peripheral arterial necrosis necessitating amputation of extremities secondary to the arterial occlusion. All patients were female, with ages ranging from 16 to 65 years. Arterial occlusion took place in the initial months of disease (median: 7 months). Only one of five patients tested for antiphospholipid antibodies had these antibodies who also had vasculitis and thrombosis in a histopathological study. Most patients presented a very benign outcome after the amputation of extremities and stayed in remission for several years. The satisfactory outcome of most patients after the vascular phenomenon allows us to consider the possibility that such a complication could be, for unknown reasons, a marker for good prognosis in SLE or, alternatively, that the aggressive therapy administrated for patients with this complication at the beginning of the disease could recover the balance of the immune system, avoiding future relapses.

Rituximab as an alternative for patients with severe systemic vasculitis refractory to conventional therapy: report of seven cases and literature review.

The greater understanding of pathophysiology and behavior of systemic vasculitis, together with the development of therapeutic regimens with increasingly better safety and efficacy profiles, dramatically changed the prognosis of patients diagnosed with these clinical entities. Recently, the use of rituximab in the treatment of patients with ANCA-associated vasculitis in randomized clinical trials showed an important alternative in selected cases, especially patients refractory or intolerant to standard therapy with cyclophosphamide and corticosteroids. This article presents the report of seven cases of systemic vasculitis successfully treated with rituximab.

Translation, cultural adaptation and validation into portuguese (Brazil) in Systemic Sclerosis Questionnaire (SySQ).

INTRODUCTION: Systemic sclerosis (SSc) is a multisystem disease, autoimmune disorder characterized by a fibroblastic disfunction, with significant impact on quality of life (QoL), measured by instruments or questionnaires that usually were formulated in other languages and in different cultural contexts. OBJECTIVE: Translate into Brazilian Portuguese, cross cultural adaptation and assess the reliability and validity of the Systemic Sclerosis Questionnaire (SySQ). METHODOLOGY: Translation and adaptation: into Portuguese and cross-cultural adaptation was performed in accordance with studies on questionnaire translation methodology into other languages. Reliability: it was analyzed using three interviews with different interviewers, two on the same day (interobserver) and the third within 14 days of the first assessment (intraobserver).Validity was assessed by correlating clinical and quality of life parameters with the domain scores of Sysc. STATISTICAL ANALYSIS: a descriptive analysis of the study sample. Reproducibility was assessed using an intraclass correlation coefficient (ICC). Internal consistency was assessed using Cronbach's alpha coefficient. To assess validity we used Spearman correlation coefficient. Five percent was the level of significance adopted for all statistical tests. RESULTS: In the evaluation of the questionnaires, the results were similar to the original questionnaire, the internal consistency ranging between 0.73 and 0.93 for each item. The interobserver reproducibility was very good for all domains (α = 0.786 to 0.983) and intraobserver agreement was considered very good for general symptoms domain (ICC = 0.916), good for musculoskeletal symptoms domain (ICC = 0.897) and cardiopulmonary domain (ICC = 0.842) and reasonable for gastrointestinal symptoms domain (ICC = 0.686). CONCLUSION: The Brazilian Portuguese version of SySQ proved to be reproducible and valid for our population, using a recognized methodology for translation and cultural adaptation of questionnaires, as well as to assess the reproducibility and validity.

Incidence of neoplasms in the most prevalent autoimmune rheumatic diseases: a systematic review.

This article is a systematic review of the literature about the coexistence of cancer and autoimmune rheumatic diseases, their main associations, cancers and possible risk factors associated, with emphasis on existing population-based studies, besides checking the relation of this occur with the use of the drugs used in the treatment of autoimmune diseases. A search was conducted of scientific articles indexed in the Cochrane / BVS, Pubmed / Medline and Scielo / Lilacs in the period from 2002 to 2012. Also consulted was the IB-ICT (Brazilian digital library of theses and Masters), with descriptors in Portuguese and English for "Systemic sclerosis", "Rheumatoid Arthritis", " Systemic Lupus Erythematosus" and "Sjögren's syndrome", correlating each one with the descriptor AND "neoplasms". The results showed that in the database IBICT a thesis and a dissertation for the descriptor SLE met the inclusion criteria, none met RA one thesis to SS. Lilacs in the database/Scielo found two articles on "Rheumatoid Arthritis" AND "neoplasms". In Pubmed/Medline the inicial search resulted in 118 articles, and 41 were selected. The review noted the relationship between cancer and autoimmune rheumatic diseases, as well as a risk factor for protection, although the pathophysiological mechanisms are not known.

Lupus erythematosus: considerations about clinical, cutaneous and therapeutic aspects.

Systemic Lupus Erythematosus is a chronic inflammatory disease with multifactorial etiology. Although clinical manifestations are varied, the skin is an important target-organ, which contributes to the inclusion of skin lesions in 4 out of the 17 new criteria for the diagnosis of the disease, according to the Systemic Lupus International Collaborating Clinics. The cutaneous manifestations of lupus are pleomorphic. Depending on their clinical characteristics, they can be classified into Acute Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus and Intermittent Cutaneous Lupus Erythematosus. Treatment is based on preventive measures, reversal of inflammation, prevention of damage to target organs and relief of adverse events due to pharmacological therapy. The most commonly used treatment options are topical, systemic and surgical treatment, as well as phototherapy. The correct handling of the cases depends on a careful evaluation of the morphology of the lesions and the patient's general status, always taking into consideration not only the benefits but also the side effects of each therapeutic proposal.

Use of rituximab as a treatment for systemic lupus erythematosus: retrospective review.

OBJECTIVE: To report the experience in three Brazilian institutions with the use of rituximab in patients with different clinical forms of lupus erythematosus systemic in activity. METHODS: The study consisted of a sample of 17 patients with LES, who were already being treated, but that at some stage of the disease showed refractory symptoms. The patients were subdivided into groups according to the clinical manifestation, and the responses for the use of rituximab were rated as complete, partial or no response. Data were collected through a spreadsheet, and used specific parameters for each group. The treatment was carried on by using therapeutic dose of 1g, and repeating the infusion within an interval of 15 days. RESULTS: The clinical responses to rituximab of the group only hematological and of the group only osteoarticular were complete in all cases. In the renal group there was a clinical complete response, two partial and one absent. In the renal and hematological group complete response, there was one death and a missing response. The pulmonary group presented a complete response and two partial. CONCLUSION: The present study demonstrated that rituximab can bring benefits to patients with lupus erythematosus systemic, with good tolerability and mild side effects; it presented, however, variable response according to the system affected.

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases

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.

[Systemic lupus erythematosus and allergy: an integrative review of the literature]. / Lupus eritematoso sistêmico e alergias: uma revisão integrativa da literatura.

OBJECTIVES: To investigate, in the literature, the existence of studies that relate the occurrence of allergic diseases in patients with Systemic Lupus Erythematosus (SLE). METHODS: For the study, we used the model of integrative literature review. This was developed in stages: selection of hypotheses or questions for review, selection of research to write the review sample, defining the characteristics of primary research that comprise the review sample, interpretation and reporting the results of the review. For the electronic search of the literature it was used databases of health sciences in general (LILACS, MEDLINE / PubMed and SciELO). We included original full articles, published between 1982 and 2012 in English, Portuguese or Spanish, to evaluate clinical and laboratory aspects of the association between SLE and allergy. RESULTS: The literature review found twenty-four articles that met the inclusion criteria previously established. Most of the studies demonstrated higher allergic diseases prevalence in SLE patients and/or their family members when compared to a control group without the disease, that suggests a possible genetic similarity between the two diseases. There was also an increase in serum IgE levels in SLE patients, which correlated with the presence of allergic reactions and disease activity in some studies. However, were observed in some studies results contrary to these. In addition, some articles have evaluated the association between sex hormones, SLE and allergies, and suggests the ability of estrogen to be related to hyperresponsiveness to endogenous or exogenous antigens. CONCLUSION: The association between allergic diseases, adverse drug reactions and increasing of serum levels of IgE and the presence of SLE remains controversial. Most of the articles analyzed in this review demonstrated an association between allergic diseases and SLE. In Addition, they showed that the increase of serum levels of IgE in patients with SLE is correlated with disease activity. After this integrative review, we conclude that there is need to expand the studies on the relation between these two diseases, for to clarify all doubts of the subject.

Fibromuscular dysplasia: a differential diagnosis of vasculitis.

Fibromuscular dysplasia (FMD) involves small- and medium-sized arteries, being a well-known cause of hypertension in young Caucasian women, when renal arteries are involved. The etiology of FMD remains unknown, despite many theories. A genetic component is suspected to exist, because the pathology affects primarily Caucasians. Association between FMD and the HLA-DRw6 histocompatibility antigen has also been described. The major sites affected are renal, cerebral, carotid, visceral, iliac, subclavian, brachial and popliteal arteries. Clinical manifestations correlate with the affected site, arterial hypertension being a frequent symptom, resulting from the involvement of the renal arteries in 60%-75% of the cases. The diagnosis of FMD is made by histopathology and/or angiography. FMD can manifest as a systemic vascular disease, mimicking vasculitis. This understanding is important because vasculitis and FMD can both have a severe clinical course, but require distinct treatments. The differential diagnosis can be difficult in face of an atypical clinical presentation or lack of histopathologic confirmation. Isolated cases of FMD have been reported mimicking the following conditions: polyarteritis nodosa, Ehlers-Danlos's syndrome, Alport's syndrome, pheochromocytoma, Marfan's syndrome, and Takayasu's arteritis. Rheumatologists should be aware of this differential diagnosis. Treatment of FMD is recommended only in symptomatic cases, and consists in revascularization, which may be either surgical or via percutaneous transluminal angioplasty. In FMD, the effects of corticotherapy can directly and rapidly harm the vascular wall, aggravating the lesions.

Recommendations of the Brazilian Society of Rheumatology for diagnosis and treatment of Chikungunya fever. Part 1 - Diagnosis and special situations / Recomendações da Sociedade Brasileira de Reumatologia para diagnóstico e tratamento da febre chikungunya. Parte 1 - Diagnóstico e situações especiais

Abstract Chikungunya fever has become a relevant public health problem in countries where epidemics occur. Until 2013, only imported cases occurred in the Americas, but in October of that year, the first cases were reported in Saint Marin island in the Caribbean. The first autochthonous cases were confirmed in Brazil in September 2014; until epidemiological week 37 of 2016, 236,287 probable cases of infection with Chikungunya virus had been registered, 116,523 of which had serological confirmation. Environmental changes caused by humans, disorderly urban growth and an ever-increasing number of international travelers were described as the factors responsible for the emergence of large-scale epidemics. Clinically characterized by fever and joint pain in the acute stage, approximately half of patients progress to the chronic stage (beyond 3 months), which is accompanied by persistent and disabling pain. The aim of the present study was to formulate recommendations for the diagnosis and treatment of Chikungunya fever in Brazil. A literature review was performed in the MEDLINE, SciELO and PubMed databases to ground the decisions for recommendations. The degree of concordance among experts was established through the Delphi method, involving 2 in-person meetings and several online voting rounds. In total, 25 recommendations were formulated and divided into 3 thematic groups: (1) clinical, laboratory and imaging diagnosis; (2) special situations; and (3) treatment. The first 2 themes are presented in part 1, and treatment is presented in part 2.

Resumo A febre chikungunya tem se tornado um importante problema de saúde pública nos países onde ocorrem as epidemias. Até 2013, as Américas haviam registrado apenas casos importados quando, em outubro desse mesmo ano, foram notificados os primeiros casos na Ilha de Saint Martin, no Caribe. No Brasil, os primeiros relatos autóctones foram confirmados em setembro de 2014 e até a semana epidemiológica 37 de 2016 já haviam sido registrados 236.287 casos prováveis de infecção pelo chikungunya vírus (CHIKV), 116.523 confirmados sorologicamente. As mudanças ambientais causadas pelo homem, o crescimento urbano desordenado e o número cada vez maior de viagens internacionais têm sido apontados como os fatores responsáveis pela reemergência de epidemias em grande escala. Caracterizada clinicamente por febre e dor articular na fase aguda, em cerca de metade dos casos existe evolução para a fase crônica (além de três meses), com dor persistente e incapacitante. O objetivo deste trabalho foi elaborar recomendações para diagnóstico e tratamento da febre chikungunya no Brasil. Para isso, foi feita revisão da literatura nas bases de dados Medline, SciELO e PubMed, para dar apoio às decisões tomadas para definir as recomendações. Para a definição do grau de concordância foi feita uma metodologia Delphi, em duas reuniões presenciais e várias rodadas de votação on line. Foram geradas 25 recomendações, divididas em três grupos temáticos: (1) diagnóstico clínico, laboratorial e por imagem; (2) situações especiais e (3) tratamento. Na primeira parte estão os dois primeiros temas e o tratamento na segunda.

Recommendations of the Brazilian Society of Rheumatology for the diagnosis and treatment of chikungunya fever. Part 2 - Treatment / Recomendações da Sociedade Brasileira de Reumatologia para diagnóstico e tratamento da febre chikungunya. Parte 2 - Tratamento

Abstract Chikungunya fever has become an important public health problem in countries where epidemics occur because half of the cases progress to chronic, persistent and debilitating arthritis. Literature data on specific therapies at the various phases of arthropathy caused by chikungunya virus (CHIKV) infection are limited, lacking quality randomized trials assessing the efficacies of different therapies. There are a few studies on the treatment of musculoskeletal manifestations of chikungunya fever, but these studies have important methodological limitations. The data currently available preclude conclusions favorable or contrary to specific therapies, or an adequate comparison between the different drugs used. The objective of this study was to develop recommendations for the treatment of chikungunya fever in Brazil. A literature review was performed via evidence-based selection of articles in the databases Medline, SciELO, PubMed and Embase and conference proceedings abstracts, in addition to expert opinions to support decision-making in defining recommendations. The Delphi method was used to define the degrees of agreement in 2 face-to-face meetings and several online voting rounds. This study is part 2 of the Recommendations of the Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia - SBR) for the Diagnosis and Treatment of chikungunya fever and specifically addresses treatment.

Resumo A febre chikungunya tem se tornado um importante problema de saúde pública nos países onde ocorrem as epidemias, visto que metade dos casos evolui com artrite crônica, persistente e incapacitante. Os dados na literatura sobre terapêuticas específicas nas diversas fases da artropatia ocasionada pela infecção pelo vírus chikungunya (CHIKV) são limitados, não existem estudos randomizados de qualidade que avaliem a eficácia das diferentes terapias. Há algumas poucas publicações sobre o tratamento das manifestações musculoesqueléticas da febre chikungunya, porém com importantes limitações metodológicas. Os dados atualmente disponíveis não permitem conclusões favoráveis ou contrárias a terapêuticas específicas, bem como uma adequada avaliação quanto à superioridade entre as diferentes medicações empregadas. O objetivo deste trabalho foi elaborar recomendações para o tratamento da febre chikungunya no Brasil. Foi feita uma revisão da literatura com seleção de artigos baseados em evidência, nas bases de dados Medline, SciELO, PubMed e Embase e de resumos de anais de congressos, além da opinião dos especialistas para dar apoio às decisões tomadas para definir as recomendações. Para a definição do grau de concordância foi feita uma metodologia Delphi, em duas reuniões presenciais e várias rodadas de votação on line. Este artigo refere-se à parte 2 das Recomendações da Sociedade Brasileira de Reumatologia para Diagnóstico e Tratamento da Febre Chikungunya, que trata especificamente do tratamento.