How Did Patients Living With Immune-Mediated Rheumatic Diseases Face the Beginning of the COVID-19 Pandemic in Brazil? Results of the COnVIDa Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has brought additional burden to patients living with immune-mediated rheumatic diseases (IMRDs), especially at the beginning of 2020, for which information for this population is lacking. METHODS: COnVIDa is a cross-sectional study on patients with IMRD from all regions of Brazil who were invited to answer a specific and customized Web questionnaire about how they were facing the COVID-19 pandemic, especially focusing on health care access, use of medications, and patient-reported outcomes related to IMRD activity. The questionnaire was applied from June 1 to 30, 2020. RESULTS: In total, 1722 of 2576 patients who answered the Web questionnaire were included in the final analysis. Participants were most frequently women, 56% were between 31 and 50 years old, and most (55%) has private health insurance. The most commonly reported IMRD was rheumatoid arthritis (39%), followed by systemic lupus erythematosus (28%). During the study period, 30.7% did not have access to rheumatology consultations, and 17.6% stopped chronic medications. Telemedicine was reported in 44.8% of patients. CONCLUSION: COnVIDa demonstrated a negative impact on health care access and treatment maintenance of patients living with IMRD during the COVID-19 pandemic. However, it also presented an uptake of telemedicine strategies. Data presented in this study may assist future coping policies.

Performance of the Rheumatoid Arthritis Disease Activity Index in the Assessment of Disease Activity in Rheumatoid Arthritis-Findings From the REAL Study.

BACKGROUND/OBJECTIVE: Although telemedicine use has been under discussion for decades, this topic has gained unprecedented importance during the COVID-19 pandemic. The Rheumatoid Arthritis Disease Activity Index (RADAI) is a user-friendly tool, fully self-administered, to assess rheumatoid arthritis (RA) disease activity. The aim of this study was to compare the performance of RADAI with other disease activity indices, functional status, and inflammatory markers in a large cohort of RA patients. METHODS: We assessed the concurrent validity of RADAI against Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 Joints-C-reactive protein, Disease Activity Score in 28 Joints-erythrocyte sedimentation rate, Simplified Disease Activity Index, and physician assessment of disease activity and the correlation of RADAI with Health Assessment Questionnaire-Disability Index and inflammatory markers at the REAL Study baseline. We also evaluated the correlation of the change in RADAI and the change in CDAI over a 6-month follow-up. RESULTS: From the 1115 patients included in the REAL Study, 1113 had RADAI scores in the first assessment. At baseline, correlations between RADAI and other disease activity indices were strong, ranging from 0.64 (comparison with physician assessment) to 0.79 (comparison with CDAI). Correlation between the change in RADAI score over the 6 months of follow-up and the change in CDAI score over the same period was moderate/strong for the overall group and within the stratified analyses. CONCLUSION: The strong correlation of RADAI with other well-established tools for disease activity measurement reassures its use with RA patients' follow-up, especially in this new era of telemedicine.

Enhanced IL-6 and IL-12B Gene Expression After SARS-CoV-2 Infection in Leprosy Patients May Increase the Risk of Neural Damage.

Experts have called attention to the possible negative impact of the coronavirus disease 2019 (COVID-19)-related cytokine storm syndrome on the progression of leprosy-related disabilities. We assessed the frequency of reactional states in patients co-infected with Mycobacterium leprae and severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS-CoV-2). We consecutively included patients during the first peak of the COVID-19 epidemic in Brazil and analyzed the expressions of genes encoding interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12A, IL-12B, and tumor necrosis factor-α in peripheral blood mononuclear cells. We included 64 leprosy patients and 50 controls. Twelve of the leprosy patients and 14 of the controls had been diagnosed with COVID-19. Co-infection was associated with increased IL-6 (P = 0.043) and IL-12B (P = 0.017) expression. The median disability grades were higher for leprosy/COVID-19 patients; however, the difference was not significant (P = 0.194). Patients co-infected with M. leprae and SARS-CoV-2 may experience a higher-grade proinflammatory state.

Microbes, helminths, and rheumatic diseases.

There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood. The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.

Opportunistic tropical infections in immunosuppressed patients.

Autoimmune and autoinflammatory diseases are associated with severe morbidity, and represent an impactful health and economic burden worldwide. The treatment of these diseases can include a course with detrimental side effects. Immunosuppression increases the risk of opportunistic infections, but in some cases, the abrupt discontinuation of these medications can result in immune reconstitution inflammatory syndrome. Special attention must be directed to endemic tropical infections, such as leishmaniasis, Chagas disease, malaria, arbovirosis, yellow fever, leprosy, paracoccidioidomycosis, disseminated strongyloidiasis, and ectoparasitosis. These endemic diseases of developing countries can be considered as possible emerging diseases in developed regions partially because of environmental factors and migration. In the present article, we aim to review the evidence-based aspects of the most important opportunistic tropical infections in immunosuppressed patients. We also aim to review the important aspects of vaccination, chemical prophylaxis, and treatment for these infections in people with medication-induced immunosuppression.

Parasites in Rheumatoid Arthritis: Imminent Threat or Protective Effect?

Parasitic infections are among the oldest and most common infections in humans. Host defense alterations caused by autoimmune diseases or immunosuppressive drugs can cause modifications of the symptoms: indolent parasites can be reactivated, asymptomatic patients may experience new symptoms, or mild or moderate symptoms can become serious and, rarely, may lead to death. In recent years, new drugs have been used in the treatment of rheumatoid arthritis (RA), causing a greater level of immunosuppression and, therefore, more concerns regarding the risk of serious parasitic diseases. Of note, experimental studies have demonstrated that the immunomodulation induced by infection with helminths can minimize the occurrence and severity of rheumatoid arthritis. Products derived from helminths (such as glycoprotein ES-62) can exert favorable effects in RA patients via their anti-inflammatory actions. Greater knowledge of these substances may serve as a basis for the development of new treatments for RA. The full impact of parasitic diseases on patients with rheumatoid arthritis remains controversial, and further studies are warrented.

Tomografia por emissão de pósitrons com FDG-18F na avaliação de pacientes com artrite reumatoide - revisão sistemática / Positron emission tomography with 18F-FDG in the evaluation of patients with rheumatoid arthritis - a systematic review

Introdução A artrite reumatoide (AR) é uma doença caracterizada pela inflamação da membrana sinovial. Diversos autores têm investigado o papel da tomografia por emissão de pósitrons (PET) com flúor-18 (FDG-18F) na AR. Objetivos Revisão sistemática da literatura atual sobre o papel do PET com FDG-18F no diagnóstico, determinação da atividade da doença e avaliação da resposta ao tratamento em pacientes com AR. Métodos Foram realizadas buscas nas bases de dados Medline, Biblioteca Cochrane, Lilacs, Pubmed e Scopus nos idiomas português, inglês e espanhol, utilizando as palavras-chave «artrite reumatoide¼, «sinovite¼, «FDG¼, «PET¼, «metabolismo glicolítico¼ e «atividade da doença¼. Resultados 142 artigos foram inicialmente identificados, dos quais apenas 40 relacionavam-se diretamente ao tema. Foram selecionados 12 artigos originais e três relatos de caso que preenchiam os critérios de inclusão. Discussão A presença de fibroblastos e macrófagos ativados no pannus é responsável pela intensa captação periarticular de FDG-18F. Os padrões de captação não permitem o diagnóstico diferencial com outras artrites. A intensidade de captação e o número de articulações envolvidas são parâmetros metabólicos de atividade da doença que apresentam boa correlação com os índices compostos. Estudos longitudinais de PET têm se mostrado úteis na avaliação da resposta ao tratamento com anti-TNF. Quando realizado precocemente, PET pode predizer a resposta terapêutica. Conclusão Embora o real papel dessa nova técnica na investigação da AR ainda não esteja estabelecido, PET com FDG-18F é uma ferramenta ...

Introduction Rheumatoid arthritis (RA) is a disease characterized by inflammation of the synovial membrane. Several authors have investigated the role of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (18F-FDG) in RA. Objectives To systematically review the current literature on the role of 18F-FDG PET in the diagnosis, determination of disease activity and assessment of treatment response in patients with RA. Methods Searches were conducted in Medline, Cochrane Library, Lilacs, Pubmed and Scopus in Portuguese, English and Spanish languages, using the keywords «rheumatoid arthritis¼, «synovitis¼, «FDG¼, «PET¼, «glycolytic metabolism¼ and «disease activity¼. Results One hundred and forty-two articles were initially identified, of which only 40 were related directly to the subject. Twelve original articles and three case reports that met the inclusion criteria were selected. Discussion The presence of activated macrophages and fibroblasts in pannus are responsible for the intense periarticular uptake of 18F-FDG. The uptake patterns do not allow the differential diagnosis with other arthritides. The uptake intensity and the number of joints involved are metabolic parameters of disease activity that correlate well with the composite indices. Longitudinal studies of PET have proven useful in assessing the response to treatment with anti-TNF. When performed early, PET can predict the therapeutic response. Conclusion Although the actual role of this new technique for the investigation of RA is not yet established, 18F-FDG PET is a promising tool in determining the activity and prediction of response to treatment of patients with RA. .

Leishmaniasis during anti-tumor necrosis factor therapy: report of 4 cases and review of the literature (additional 28 cases).

OBJECTIVE: To describe the development of 4 new cases of leishmaniasis in patients receiving anti-tumor necrosis factor-α (anti-TNF) agents and review the pertinent literature. METHODS: Chart review of the 4 cases and MEDLINE search for additional reported cases. RESULTS: All reported cases, including ours, came from endemic areas. The infection was detected on an average of 23.5 months after the initiation of anti-TNF therapy. The majority of cases had the classical clinical presentation. The biological therapy was suspended in 21 cases. The results were successful for leishmaniasis therapy in all cases. In 10 cases it was possible to reintroduce anti-TNF agents. On follow-up it was observed that there was an infection relapse in 3 cases. CONCLUSIONS: The present study shows that leishmaniasis, in its several clinical forms, should be included in the differential diagnosis of possible infections involving patients under use of aTNF therapy. Endemic disease under geographic expansion, easy international displacement and intense human migratory flows certainly represents a risk of this infection in an increasing universe of people which includes the immunosuppressed patients. Cutaneous lesions, prolonged fever, splenomegaly, and pancytopenias, the main clinical-laboratory findings of leishmaniasis, can also be present in autoimmune rheumatic disease, thus leading to delayed diagnosis and treatment of the parasitic disease. The diagnosis depends basically on a high suspicion index, being confirmed with the identification of the protozoan. The classic treatment of the infection when instituted is associated with complete recovery. It is important to point out that all cases reported so far had either originated from or been recently in regions regarded as endemic of leishmaniasis.

[Reactive arthritis in HIV-infected patients: immunopathogenic aspects]. / Artrite reactiva em pacientes infectados pelo HIV: aspectos imunopatogênicos.

Reactive arthritis ReA is still an incompletely understood rheumatic disorder whose immunopathogeny involves several mechanisms. There is an association with Class-I histocompatibility antigens HLA-B27 and history of previous gastrointestinal or genitourinary infections. The molecular mimicry between bacterial and self antigens suggests the possibility of cross reactivity as a disease mechanism. The infection pandemics by the human immunodeficiency virus HIV changed the profile of the occurrence of a number of rheumatic diseases including ReA which appears to be more frequent more severe and refractory to the usual treatment for retrovirus-infected patients. The intensity of articular and extra-articular manifestations of ReA often makes the use of immunosuppressant drugs in these patients necessary. Due to the immunosuppression resulting from the retrovirosis itself the treatment becomes a dilemma for rheumatologists. HIV seems to play a role in the main ReA immunopathogenesis mechanisms either acting as direct arthritogenic agent or causing an immune dysfunction in the CD4 T lymphocytes T CD8 relationship leading to the deregulation in the production of cytokines or in advanced immunosuppression stages predisposing to infection by other arthritogenic pathogens. The use of highly active anti-retroviral therapy HAART has changed the profile of rheumatic events and the immunopathogeny of the HIV ReA association. The understanding of the basic ReA immunopathogenic mechanisms in HIV-infected patients is vital in the attempt of elucidating many still existing questions.