Rafaela Silva Guimarães Gonçalves

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.

Recomendações da Sociedade Brasileira de Reumatologia para diagnóstico e tratamento da febre chikungunya. Parte 2 – Tratamento

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 recommen-s, 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 S440 r e v b r a s r e u m a t o l . 2 0 1 7;5 7(S 2):S438–S451 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.

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.

Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations.

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients. Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR. Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p < 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p = 0.02), digital ulcers (p = 0.02), lung fibrosis (p < 0.0001), positive antitopoisomerase I (p = 0.03), and higher modified Rodnan score (p = 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin. Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

Correction to: Statins Inhibit Cytokines in a Dose-Dependent Response in Patients with Systemic Sclerosis

One of the author’s surname was incorrect. Anderson Ferreira de Almeida should be captured as Anderson Rodrigues de Almeida. The correct name is now presented above.

IL-17 and related cytokines involved in systemic sclerosis: Perspectives

Abstract Systemic sclerosis (SSc) is a multisystemic, complex, and rare disease of connective tissue, with high morbidity and mortality, and without specific treatment. The disease is characterized by three main principles: vascular disease, autoantibody production and inflammation, and fibrosis. Since it is well defined that SSc is characterized by elevated production of TGF-β, IL-6, and IL-1, all of them cytokines related to Th17 differentiation, the hypothesis is that this disease may be strongly related to a polarization of the immune response towards the Th17 pathway. Considering the importance of a better understanding of the pathophysiology of Th17 pathway in SSc, this article aims to propose an update for a better understanding of current knowledge on main cytokines secreted by the Th17 cells (IL-17 A, IL-21, and IL-22) and the future prospects in the current disease.

SAT0562 Chikungunya fever in patients with prior rheumatic diseases: is it more severe?

Background Chikungunya fever (CF) is an infectious disease caused by a RNA virus and its transmission occurs by the inoculation of the virus by the female bite of Aedes aegypti mosquito. In Brazil, where the vetor is endemic, the virus rapidly disseminated and there was an epidemic, specially in the Northeast region of the country with 263.980 notified cases in 2016. It is known that CF may have a chronic course with articular symptons, however there is not consistent data in the medical literature on CF evolution in patients with prior rheumatic diseases. Objectives To assess whether there is any difference in the characteristics of articular manifestations of CF in patients with prior inflammatory rheumatic diseases (IRD), non-inflammatory rheumatic diseases (NIRD) and controls (patients with no diagnosed prior rheumatic diseases). Methods Cross-sectional study using a database from CHIKBRASIL cohort. Patients enrolled had clinical and epidemiological characteristics of CF and were classified in three groups: IRD (rheumatoid arthritis, axial spondyloarthritis and systemic lupus erythematosus), NIRD (fibromyalgia and osteoarthritis) and controls (no prior rheumatic diseases). Results A total of 150 patients were enrolled. There were 55 patients with IRD, 40 patients with NIRD and 55 controls, paired by age and sex. There were no differences in acute phase symptoms in the groups. There a was more frequent occurrence of arthritis in patients with IRD compared to NIRD (p=0.001) and to controls (p=0.002). In 89.1% of the patients with IRD there was an underlying disease exacerbation and 74% described an expressive worsening of symptoms compared to the period prior to infection. Patients with IRD had an increase in the current dose of corticosteroids (median 10mg, IQR 10–20) compared to previous dose used (median 6mg, IQR 5–10) after the onset of CF (p=0.0007). Importantly, there was more methotrexate prescription (23.5%) in IRD group, compared to NIRD group (0, p-0.001) and to controls (3.7%, p=0.003). Conclusions Patients with IRD and CF presented significantly more arthritis compared to NIRD or to controls. CF seems to induce underlying rheumatologic disease exacerbation in patients with inflammatory disease and a more aggressive therapeutic approach might be necessary in this group of patients. Disclosure of Interest None declared

SAT0557 Chikungunya outbreak in brazil: demographic and clinical characterization of 732 patients – chikbrasil cohort

Background Chikungunya Fever (CF) is a disease characterized by acute febrile arthritis and caused by a mosquito-transmitted alphavirus. Considering the wide distribution of the vector, the presence of imported cases from 2010 and Brazilian populations susceptibility, there was a dispersal and establishment of Chikungunya virus (CHIKV) throughout the country. Since 2014, the CF has achieved a large proportion of the Brazilian population and has been responsible for the development of chronic joint symptoms in thousands of people. Objectives To describe the demographic, clinical and serological characteristics of patients from specialized Rheumatology services from northeastern Brazil, in a large, multicenter cohort. Methods Data from 732 patients in a prospective, multicenter, observational cohort conducted in six research rheumatology centers were analyzed. Patients 18 years or older who fulfilled the clinical and epidemiological Health Ministry criteria for case definition of CF were included in the study, from April to December 2016. Results From 732 patients included, 83.1% were women. The mean age was 54.1 (± 13.4) years; 92.4% lived in urban area and 58.6% had only primary education. The most common comorbidities were hypertension (43.8%), hyperlipidemia (25.3%) and diabetes mellitus (13.7%). Prior rheumatologic disease was observed in 16.4% patients, being the most frequent rheumatoid arthritis (32.5%), osteoarthritis (32.5%) and spondyloarthritis (11.7%). Arthralgia was the most frequent symptom referred by all patients; fever and fatigue were also common manifestations, being referred by 95.3% and 87.1% of patients, respectively. Arthritis occurred in 84.3%. The most frequent joint pattern involvement was polyarticular (67.8%) and the additive (84.0%). At the first appointment with the rheumatologist, 75.9% had been or were under corticosteroid use, with the average dose of 15.4 mg (±8.7) of prednisone or equivalent; was observed an median of 8 painfull joints (IQR 4–21) and arthritis was found in 73.6% patients, with an median of 2 swollen joints (IQR 0–5). The median score of patient global assessment at the time of the initial evaluation was 6 (IQR 4–8) using a 10 points visual analogue scale. After resting stiffness was referred by 86.0%, with 58.4% of these longer than 30 minutes. The most commonly prescribed medications were corticosteroids (58.3%) and hydroxychloroquine (59.1%). The serological tests for CHIKV were positive for IgM in 97.1% and for IgG in 71.7% of patients. Conclusions This is the first descriptive study of a cohort Brazilian patients with CF, with an expressive number of patients when compared to those described in the literature. Most of the features of patients in our cohort were similar to the results described in studies/cohorts published. Disclosure of Interest None declared