Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

INTRODUCTION: Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations. OBJECTIVE: To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis. METHODS: In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis. RESULTS: Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82). In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9). CONCLUSION: Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking and shared epitope alleles were correlated with anti-cyclic citrullinated peptide-antibody-positive rheumatoid arthritis. Of the risk factors, only anticyclic citrullinated peptides antibodies were independently associated with rheumatoid arthritis susceptibility

The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis

OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers). RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions

Infliximabe reduz débito cardíaco em pacientes com artrite reumatoide sem insuficiência cardíaca

OBJECTIVE: Human anti-tumor necrosis factor (TNF-α) monoclonal antibody (infliximab) is used to treat autoimmune diseases such as rheumatoid arthritis (RA). Although the risk of worsening heart failure has been described in patients under chronic treatment, the acute cardiovascular effects of this drug are unknown in RA patients without heart failure. METHODS: 14 RA patients with normal echocardiography and no history of heart failure were evaluated during the 2-hour infliximab (3-5 mg/kg) infusion period, using a noninvasive hemodynamic beat-to-beat system (Portapres). Stroke volume (SV); systolic, diastolic and mean blood pressures (SBP, DBP and MBP, respectively); cardiac output (CO); heart rate (HR); and total peripheral vascular resistance (PVR) were recorded. All patients also received saline infusion instead of infliximab as a control. Significant differences in hemodynamic parameters were determined using Tuckey's test. All values were expressed as mean ± standard deviation (SD). RESULTS: Fourteen RA patients (6M/8F) with mean age of 47.2 ± 8.8 years were evaluated. A significant decrease was found in cardiac output and stroke volume (7.04 ± 2.3 to 6.12 ± 2.1 l/min and 91 ± 29.0 to 83 ± 28.8 mL/beat, respectively) after infliximab infusion. Although not statistically significant, a progressive increase was detected in SBP, DBP and total PVR during infusion. Saline infusion did not cause significant hemodynamic changes in the same group of RA patients. No adverse effects were observed during the infusion period. CONCLUSION: Acute infliximab administration decreased cardiac output due to low stroke volume in RA patients without heart disease. The results also demonstrated that, in spite of its negative inotropic effect, infliximab enhanced BP, probably by increasing PVR.OBJETIVO: O inibidor de fator de necrose tumoral (TNF-α) infliximabe é usado no tratamento de doenças autoimunes como a artrite reumatoide (AR). Embora o risco de piora de insuficiência cardíaca em pacientes submetidos a tratamento crônico tenha sido descrito, os efeitos cardiovasculares agudos da infusão desta droga em pacientes com AR sem insuficiência cardíaca são desconhecidos. MÉTODOS: Pacientes com AR e ecocardiogramas normais e sem antecedentes de insuficiência cardíaca foram avaliados durante o período de infusão de infliximabe (3-5mg/kg), de 2 horas, utilizando um sistema de monitoramento hemodinâmico não invasivo batimento-a-batimento (Portapres). As variáveis avaliadas foram: volume sistólico (VS), pressão arterial sistólica, diastólica e média (PAS, PAD e PAM, respectivamente), débito cardíaco (DC), frequência cardíaca (FC) e resistência vascular periférica total (RVPT). Todos os voluntários também receberam infusão de soro fisiológico (SF) como estudo controle. Estatísticas foram avaliadas usando o teste de Tuckey. Os valores estão expressos em média ± desvio-padrão. RESULTADOS: Catorze pacientes (6M/8F), com idade média de 47,2 ± 8,8 anos, foram avaliados. Reduções significativas no débito cardíaco e volume sistólico foram encontradas após a infusão do infliximabe (7,04 ± 2,3 a 6,12 ± 2,1 L/min e 91 ± 29,0 a 83 ± 28,8 mL/batimento, respectivamente). Embora não estatisticamente significante, detectaram-se aumentos progressivos na PAS, PAD e RVPT durante a infusão. A infusão controle de SF não causou mudanças hemodinâmicas significativas nos pacientes estudados. Não foram observados efeitos adversos no período de infusão. CONCLUSÃO: A administração de infliximabe reduz agudamente o débito cardíaco devido a redução no volume sistólico em pacientes com AR sem insuficiência cardíaca. Nossos resultados mostram que, apesar do efeito inotrópico negativo, o infliximabe elevou a pressão arterial, provavelmente devido ao aumento na RVPT.698702Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Management of Nail Disease in Patients With Psoriatic Arthritis : An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations

Copyright © 2023 by the Journal of Rheumatology. Publisher Copyright: Copyright © 2023 by the Journal of Rheumatology.OBJECTIVE: Nail psoriasis is common, impairs fine motor finger functioning, affects cosmesis, and is associated with a lower quality of life. This review updates the previous Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for nail psoriasis. METHODS: This systematic literature review of the PubMed, MEDLINE, Embase, and Cochrane databases examined the updated evidence since the last GRAPPA nail psoriasis treatment recommendations published in 2014. Recommendations are based on preformed PICO (Patient/Population - Intervention - Comparison/Comparator - Outcome) questions formulated by an international group of dermatologists, rheumatologists, and patient panel members. Data from this literature review were evaluated in line with Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. RESULTS: Overall, there is insufficient evidence to make any recommendation for the use of topical corticosteroids, topical calcipotriol, topical tazarotene, topical cyclosporine, dimethyl fumarates/fumaric acid esters, phototherapy, and alitretinoin. There is a low strength of evidence to support the use of calcipotriol and corticosteroid preparations, topical tacrolimus, oral cyclosporine, oral methotrexate, intralesional corticosteroids, pulsed dye laser, acitretin, Janus kinase inhibitors, and apremilast. CONCLUSION: The highest strength of supporting evidence is for the recommendation of biologic agents including tumor necrosis factor inhibitors, and interleukin 12/23, 17, and 23 inhibitors.Peer reviewe

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. 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

High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID-19 : first results of ReumaCoV Brasil registry

Objectives To evaluate risk factors associated with unfavourable outcomes: emergency care, hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death in patients with immune-mediated rheumatic disease (IMRD) and COVID-19. Methods Analysis of the first 8 weeks of observational multicentre prospective cohort study (ReumaCoV Brasil register). Patients with IMRD and COVID-19 according to the Ministry of Health criteria were classified as eligible for the study. Results 334 participants were enrolled, a majority of them women, with a median age of 45 years; systemic lupus erythematosus (32.9%) was the most frequent IMRD. Emergency care was required in 160 patients, 33.0% were hospitalised, 15.0% were admitted to the ICU and 10.5% underwent mechanical ventilation; 28 patients (8.4%) died. In the multivariate adjustment model for emergency care, diabetes (prevalence ratio, PR 1.38; 95% CI 1.11 to 1.73; p=0.004), kidney disease (PR 1.36; 95% CI 1.05 to 1.77; p=0.020), oral glucocorticoids (GC) (PR 1.49; 95% CI 1.21 to 1.85; p50 years (PR 1.89; 95% CI 1.26 to 2.85; p=0.002), no use of tumour necrosis factor inhibitor (TNFi) (PR 2.51;95% CI 1.16 to 5.45; p=0.004) and methylprednisolone pulse therapy (PR 2.50; 95% CI 1.59 to 3.92; p<0.001); for ICU admission, oral GC (PR 2.24; 95% CI 1.36 to 3.71; p<0.001) and pulse therapy with methylprednisolone (PR 1.65; 95% CI 1.00 to 2.68; p<0.043); the two variables associated with death were pulse therapy with methylprednisolone or cyclophosphamide (PR 2.86; 95% CI 1.59 to 5.14; p<0.018). Conclusions Age >50 years and immunosuppression with GC and cyclophosphamide were associated with unfavourable outcomes of COVID-19. Treatment with TNFi may have been protective, perhaps leading to the COVID-19 inflammatory process

Association of Epstein-Barr virus with anti-CCP antibodies, the shared epitope alleles and smoking in Brazilian patients with rheumatoid arthritis

Orientadores: Manoel Barros Bértolo, Lilian Tereza Lavras CostallatTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A etiopatogenia da Artrite Reumatoide (AR) envolve fatores genéticos, imunológicos e ambientais que interagem entre si. Os principais fatores de risco estudados são a presença dos alelos do epítopo compartilhado (shared epitope- SE), dos anticorpos anti-peptídeos cíclicos citrulinados (anti-CCP) e do tabagismo. Há evidências que o Epstein-Barr vírus (EBV), ao interagir com esses fatores de risco, possa causar uma resposta imune anômala em indivíduos susceptíveis. Essas interações também podem contribuir para o desenvolvimento da AR. O objetivo principal desse estudo é estabelecer se há uma associação entre o EBV com os alelos do SE, os anticorpos anti-CCP e o tabagismo em pacientes brasileiros com AR. Os objetivos secundários são: avaliar a correlação entre os alelos do SE, os anticorpos anti-CCP e o tabagismo; detectar a exposição ao EBV e quantificar sua carga viral e estimar o risco de cada fator estudado para o desenvolvimento da AR nessa casuística. Nesse estudo caso-controle, incluímos 140 pacientes brasileiros com AR e 143 controles saudáveis; pareados por idade, sexo e etnia. Foi feita uma caracterização clínico-laboratorial da casuística. Foram realizadas a genotipagem para identificar os alelos do SE, a determinação dos anticorpos anti-CCP pelo método de ELISA e coletada a história de tabagismo de todos os sujeitos da pesquisa. Para avaliar a exposição ao EBV, realizamos a dosagem dos anticorpos anti-Epstein-Barr Nuclear Antigen 1 (anti-EBNA1). Para quantificar a carga viral do EBV, realizamos o método quantitativo da reação em cadeia polimerase em tempo real ou real-time PCR. A análise comparativa entre os grupos mostrou uma positividade significativamente maior para os alelos do SE, anticorpos anti-CCP e tabagismo no grupo de pacientes. A análise dos anticorpos anti-EBNA1 mostrou uma positividade alta, tanto em pacientes como em controles, sem diferença significativa. Entretanto, a quantificação da carga viral pela PCR em tempo real mostrou-se muito maior em pacientes do que em controles (p<0.001). As análises associativas dos anticorpos anti-EBNA1 com os outros fatores estudados não se mostraram significativas; assim como as análises associativas da carga viral do EBV pela PCR em tempo real. A positividade do anti-CCP foi maior em pacientes com os alelos do SE que são tabagistas ou ex-tabagistas (p=0.038). Nas análises de regressão logística, a variável com maior risco para o desenvolvimento da AR foi a positividade dos anticorpos anti-CCP. Apesar dos pacientes com AR apresentarem uma carga viral do EBV aumentada, esse estudo não conseguiu associá-la aos demais fatores de risco estudados. Sugerimos que esses achados possam ocorrer devido a um controle deficitário do EBV em pacientes com AR, mas que não está relacionado aos fatores de risco mais conhecidos da doença. A imunidade celular defeituosa dos pacientes com AR dificulta o controle de uma infecção latente do vírus. Portanto, não é possível estabelecer uma relação causal direta entre o EBV e a ARAbstract: The pathogenesis of rheumatoid arthritis (RA) involves genetic, immunological and environmental factors. The main risk factors are the presence of the shared epitope alleles (shared epitope- SE), anti-cyclic citrullinated peptide antibodies (Anti-CCP) and smoking. There is evidence that the Epstein-Barr virus (EBV), when interacts with these risk factors, may cause an abnormal immune response in susceptible individuals. These interactions may contribute to the development of RA. The main objective of this study is to establish whether there is an association between EBV and alleles of SE, anti-CCP antibodies and smoking in Brazilian patients with RA. Secondary objectives are the assessment of the correlation between alleles of SE, anti-CCP antibodies and smoking; the detection of EBV; the quantification of EBV viral load and the estimation of the likelihood of each analyzed factor for the development of RA in this sample. In this case-control study, we included 140 Brazilian patients with RA and 143 healthy controls; matched for age, sex and ethnicity. We performed a clinical and laboratory characterization of the sample. Genotyping was performed to identify SE alleles, anti-CCP antibodies were examined by ELISA and smoking information was collected from all subjects. To assess the exposure to EBV, we examined anti-Epstein-Barr Nuclear Antigen 1 (anti-EBNA1) antibodies. To quantify the viral load of EBV, we performed the quantitative method of polymerase chain reaction in real time or real-time PCR. The comparative analysis between groups showed a significantly higher positivity for the alleles of SE, anti-CCP antibodies and smoking in patients. The analysis of anti-EBNA1 antibodies showed a high positivity, both in patients and in controls, with no significant difference. However, the quantification of viral load by real-time PCR proved to be much higher in patients than in controls (p <0.001). Associative analysis of anti-EBNA1 antibodies with other factors studied were not significant; as well as the association analyzes of the EBV viral load by PCR in real time. The positivity of anti-CCP antibodies was higher in patients with SE alleles which are smoker or ex-smoker (p = 0.038). In logistic regression analyzes, the variable with higher risk for RA was the positivity of anti-CCP antibodies. Although patients with RA present an increased EBV viral load, this study did not link EBV to the other risk factors studied. We suggest that these findings may be due to a deficient control of EBV in RA patients, which is unrelated to the better-known disease risk factors. Defective cellular immunity of patients with RA complicates the control of latent virus infection. Therefore it is not possible to establish a direct causal relationship between EBV and RADoutoradoClinica MedicaDoutor em Clínica Médic

Escore US7 modificado na avaliação de sinovite em pacientes com artrite reumatoide inicial

ResumoObjetivoAvaliar o escore US7 modificado (escore MUS7 SIN) na avaliação de pacientes com artrite reumatoide inicial (ARI). Além disso, foram examinados recessos dorsais e palmares dos punhos, bem como pequenas articulações das mãos e dos pés, para o diagnóstico de sinovite, mediante uma avaliação global das articulações.MétodosA amostra do estudo compreendeu 32 pacientes tratados para artrite, com 13 meses como duração média da doença. Foi utilizado um aparelho de ultrassonografia (US) com transdutor de alta frequência. As mãos dos participantes também foram radiografadas e analisadas pelo escore de Larsen.ResultadosNas 832 articulações examinadas, detectou‐se sinovite em 173 (20,79%), tenossinovite em 22 (4,91%) e erosões em três (1,56%). A sinovite foi predominantemente detectada no recesso dorsal (73,38%) das articulações MCF e IFP, quando comparado com o recesso palmar (26%). A presença de sinovite nas articulações avaliadas teve correlação com os resultados clínicos (HAQ‐DI, DAS28), laboratoriais (anti‐PCC, FR, PCR) e ultrassonográficos (r = 0,37 a r = 0,42; p = 0,04 a p = 0,003). Encontramos correlação do escore MUS7 SIN para US na técnica da escala de cinzas (gray scale) ou na técnica de Doppler de amplitude (power Doppler) com os valores do instrumento DAS28 (PCR) (r = 0,38; p = 0,0332) e com os resultados da PCR (r = 0,39; p = 0,0280), respectivamente.ConclusãoO recesso dorsal, o punho e as pequenas articulações podem ser considerados como locais importantes para a detecção de sinovite pelo escore MUS7 SIN em pacientes com ARI.AbstractObjectiveTo evaluate the modified US7 score (MUS7 score SYN) in the assessment of patients with early rheumatoid arthritis (ERA). In addition, dorsal and palmar recesses of the wrists as well as of small joints of the hands and feet were examined for the presence of synovitis by means of a global assessment of joints.MethodsThe study sample comprised 32 patients treated for arthritis, with an average disease duration of 13 months. An ultrasound machine with high frequency transducer was used. Hands were also X‐rayed and analysed by Larsen score.ResultsOut of the 832 examined joints, synovitis was detected in 173 (20,79%), tenosynovitis in 22 (4,91%), and erosions in 3 (1,56%). Synovitis was predominantly detected in the dorsal recess (73,38%) of MCP and PIP joints, when compared with palmar recess (26%). The presence of synovitis in the joints evaluated correlated with clinical (HAQ‐DI, DAS28), laboratory (ACPA, RF, CRP), and ultrasound results (r = 0,37 to r = 0,42; p = 0,04 to p = 0,003). We found correlation of the MUS7 score SYN of the gray scale US or of the power Doppler US with DAS28 (PCR) values (r = 0,38; p = 0,0332), and with CRP results (r = 0,39; p = 0,0280), respectively.ConclusionThe dorsal recess, the wrist, and small joints can be considered as important sites to detect synovitis by the MUS7 score SYN in patients with ERA

Pulmonary sarcoidosis induced by anti–tumor necrosis factor therapy a paradoxical effect

Paradoxical effects or reactions to anti–tumor necrosis factor (anti-TNF) therapy are defined by the onset or exacerbation of a certain condition following a treatment regimen for the same condition.1 An increasing number of cases of noninfectious pulmonary granulomatous disease secondary to anti-TNF therapy have been described.2–4 We present here the case of a young woman who was treated with anti-TNF therapy for ankylosing spondylitis and then subsequently developed pulmonary sarcoidosis. In view of the effectiveness of anti-TNF agents in the treatment of sarcoidosis, these cases are also reported to be paradoxical effects.5 Rheumatologists should be aware of the potential for these paradoxical reactions such as sarcoidosis presenting after anti-TNF therapy2612324etanercept; infliximab; tumor necrosis factor inhibitor; adult;; Bath ankylosing spondylitis disease activity index; bronchoscopy; case report; clinical article; computer assisted tomography; drug efficacy; female; granulomatosis; histopathology; human; human tissue; Letter; low back pain; lung biopsy; lung lavage; lung sarcoidosis; peripheral lung lesion; priority journal