Translation, transcultural adaptation into Brazilian Portuguese and concurrent validity of the rheumatoid arthritis assessment scale (RAKAS-13/Brazil)

Abstract Background Knowledge of patients about Rheumatoid Arthritis (RA) is a necessary aspect to better approach self-management support in a patient-centered manner. The research instrument known as the Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS), consisting of 13 items, is simple, reliable and reproducible, and can be applied in both clinical practice and research protocols. Objectives This study aimed to translate and culturally adapt the RAKAS vocabulary into Brazilian Portuguese and to evaluate its concurrent validity. Methods The RAKAS was translated into Brazilian Portuguese and administered to 52 elderly women with RA recruited between May 2021 and May 2022. Concurrent validity was assessed using the Spearman's correlation coefficient between RAKAS and Patient Knowledge Questionnaire (PKQ). Results The participants considered RAKAS-13/BRAZIL easy to understand and did not report any doubts in answering the final version. Concurrent validity of the RAKAS-13/BRAZIL was low compared to the PKQ (ρ = 0.283, p = 0.038). Conclusion The Brazilian Portuguese version of the RAKAS (RAKAS-13/BRASIL) proved to be a questionnaire that was easy and quick to administer to assess patient knowledge about Rheumatoid Arthritis, despite its low correlation with the PKQ in the present study.

Effect of Dioscorea villosa extract and the phytoestrogen diosgenin on ovariectomized mice with zymosan-induced arthritis

Abstract Humans are exposed to natural compounds such as phytoestrogens primarily through diet and supplements. These compounds promote health by alleviating the symptoms and illnesses associated with menopause and arthritis. Diosgenin (DSG) occurs naturally in plants such as Dioscorea villosa (DV) and binds to estrogen receptors, so it may have similar effects to this hormone, including against arthritis. Thus, we investigated the effect of chronic treatment with dry extract of DV and its phytoestrogen DSG on ovariectomized mice with arthritis. We found that dry extract of Dioscorea villosa (DV) contains the phytoestrogen diosgenin (DSG) in its composition. Furthermore, arthritic mice treated with DV and DSG showed reduced neutrophil accumulation in the articular cartilage. Also, the dry extract of DV administered orally (v.o) did not alter the leukocyte count in the joints or promote changes in the reproductive tract. However, DSG altered these parameters, with possible beneficial effects by reducing symptoms related to reproductive aging. Thus, oral treatment with dry extract of DV and subcutaneous (s.c) treatment with DSG showed promise by acting against inflammation caused by arthritis and reducing symptoms in the reproductive tract due to menopause.

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive

Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort. .

Clinical significance of long non-coding RNA NORAD in rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. Methods Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. Results NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. Conclusions There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

Vacunación contra el SARS-CoV-2 en pacientes paraguayos con artritis reumatoide

Introducción: La vacunación en poblaciones expuestas a mayor riesgo de enfermedad grave y muerte consecuentes a la infección por SARS-CoV-2, ha generado un gran impacto en la salud pública mundial. Indudablemente, el beneficio ha sido evidenciado mayormente en personas con comorbilidades crónicas, donde la artritis reumatoide (AR) juega un rol importante. Objetivo: Analizar la vacunación contra Sars-CoV-2 en pacientes paraguayos con AR, durante la pandemia COVID-19. Métodos: Se realizó un estudio multicéntrico, en el que se analizó transversalmente a una cohorte de pacientes con AR, durante el periodo de octubre a diciembre del año 2022. Para el estudio se registraron variables clínico-epidemiológicas y relacionadas con la vacunación (i.e. acceso a la vacunación, tipo, número de dosis). Se realizó un análisis descriptivo de las variables con el software R-4.3.2. Resultados: Se incluyeron 568 pacientes, 84,1% eran mujeres, con un promedio de edad de 55,5±13,9 años. El 88,7% (504) pacientes, recibieron al menos una dosis de vacuna contra SARS-CoV-2. 85% (483) recibieron dos dosis, mientras que el 60,9% (344) pacientes recibieron el primer refuerzo, y 21,2% el segundo refuerzo. Conclusiones: En esta serie de pacientes paraguayos con AR el porcentaje de vacunación contra SARS-CoV-2 fue más elevado que el registrado en la población general del país. Esto podría estar relacionado con la prioridad de esta población para acceder a las vacunas y a la insistencia de sus médicos en completar el esquema de vacunación.

Introduction: Vaccination in populations exposed to increased risk of severe disease and death consequent to SARS-CoV-2 infection has generated a major impact on global Public Health. Certainly, the benefit has been evidenced mostly in people with chronic comorbidities, where rheumatoid arthritis (RA) plays an important role. Objective: To analyze vaccination against Sars-CoV-2 in paraguayan patients with rheumatoid arthritis (RA) during the COVID19 pandemic. Methods: A multicenter study was carried out, in which a cohort of patients with RA was analyzed cross-sectionally, during the period from October to December 2022. For the study, clinical-epidemiological and vaccination-related variables were recorded (i.e. access to vaccination, type, number of doses). A descriptive analysis of the variables was carried out with the R-4.3.2 software. Results: 568 patients were included, 84.1% were female, with an average age of 55.5±13.9 years. 88.7% (504) patients received at least one dose of SARS-CoV-2 vaccine, 85% (483) received two doses, while 60.9% (344) patients received the first booster, and 21.2% the second booster. Conclusions: In this series of Paraguayan patients with RA the percentage of vaccination against SARS-CoV-2 was higher than that registered in the general population of the country. This could be related to the priority of this population to access vaccines and the insistence of their physicians to complete the vaccination schedule.

Actividad y discapacidad en pacientes cubanos con artritis reumatoide como factores que influyen en la sexualidad

Introducción: La artritis reumatoide es una enfermedad autoinmune de carácter inflamatorio y crónico. La afectación en la esfera sexual es frecuente, compromete a ambos sexos y se relaciona con factores como el dolor, la discapacidad y el consumo de medicamentos. Esta afectación no ha sido suficientemente abordada en la literatura a pesar de su prevalencia, y en Cuba no se han reportado hasta el momento estudios relacionados sobre este tema de investigación. Objetivo: Determinar el impacto de la artritis reumatoide en la sexualidad y su relación en la actividad y la discapacidad. Métodos: Se realizó un estudio monocéntrico, transversal, descriptivo. Se incluyeron los pacientes con un diagnóstico de artritis reumatoide en el período comprendido de septiembre de 2019 a junio de 2021. Se utilizó el cuestionario Qualisex para evaluar el impacto de la artritis reumatoide en la sexualidad. Resultados: En el estudio doscientos veintiséis pacientes fueron incluidos, la media de edad fue de 53,38 años (DE ± 12,22) el 82,7 % fueron mujeres. Al responder el autocuestionario Qualisex el 73,9 % de los sujetos presentaron afectación en la sexualidad. No se estableció una relación significativa entre la afectación en la esfera sexual y el tiempo de evolución. A diferencia de los niveles altos de actividad y discapacidad. Conclusiones: En la población estudiada se presentó afectación en la sexualidad, no obstante, esta no se relacionó con el tiempo de evolución de la artritis reumatoide. Se encontró asociación entre la actividad de la enfermedad y la capacidad funcional con la afectación en la esfera sexual.

Introduction: Rheumatoid arthritis is a chronic, inflammatory autoimmune disease. Disorders in the sexual sphere is frequent, it affects both sexes and it is related to factors such as pain, disability and medication consumption. This condition has not been sufficiently addressed in the literature despite its prevalence and in Cuba no studies related to the topic under study have been reported to date. Objective: To determine the impact of rheumatoid arthritis on sexuality and its relationship with activity and disability. Methods: A monocentric, cross-sectional and descriptive study was carried out on patients with a diagnosis of rheumatoid arthritis, from September 2019 to June 2021. The Qualisex questionnaire was used to evaluate the impact of rheumatoid arthritis on sexuality. Results: Two hundred twenty-six patients were included, the mean age was 53.38 years (SD ± 12.22) and 82.7% were women. When answering the Qualisex self-questionnaire, 73.9% of the subjects had effects in their sexuality. No significant relationship was established between the involvement in the sexual sphere and the time of evolution. Conclusions: The impact on sexuality in the studied population was not related to the duration of rheumatoid arthritis. On the other hand, an association was found between disease activity and functional capacity with effects in the sexual sphere.

Tasa de publicaciones de trabajos presentados sobre artritis reumatoidea en congresos de Reumatología / Publication rates of papers on rheumatoid arthritis submitted to Congresses of Rheumatology

Resumen Introducción: se publica una minoría de todos los trabajos presentados en los Congresos Argentinos de Reumatología (CAR). Objetivos: analizar los temas de estudio (TDE) de los trabajos sobre artritis reumatoidea (AR) presentados en los CAR y su tasa de publicación. Materiales y métodos: se analizaron todos los resúmenes sobre AR, como motivo primario de estudio, presentados en los CAR entre 2008 y 2017. Se agruparon según TDE, y se determinaron los TDE repetidos definidos como, al menos, dos estudios similares presentados sobre el mismo tema. Se determinó la tasa de publicación, el número de estudios similares por TDE, el número de centros participantes y el número de pacientes estudiados. Resultados: sobre 346 trabajos presentados, 51 (14,7%) fueron publicados. Se publicaron 14 (11,9%) de los 118 estudios sobre TDE repetidos versus 37 (16,2%) del resto de los TDE (p=0,4). Los trabajos sobre TDE repetidos no incluyeron más pacientes ni involucraron a un número mayor de centros. Se encontraron 13 TDE repetidos con al menos tres estudios similares y ningún estudio publicado. Conclusiones: solo una minoría de los trabajos sobre AR se publicó. Un tercio de los trabajos presentados en los CAR correspondió a TDE repetidos, que no mejoraron la tasa de publicación.

Abstract Introduction: only a few articles submitted to the Argentine Congress of Rheumatology (ACOR) are published. Objectives: to analyse the topics of study (TOS) and the publication rate of articles on rheumatoid arthritis (RA) submitted to the ACOR. Materials and methods: every abstract submitted to the ACOR between 2008 and 2017, whose primary research subject was RA, was analyzed and sorted according to TOS. Repeated TOS, defined as at least two similar studies on the same topic, were identified. The publication rate and the number of similar studies according to TOS, participating centers, and patients were determined. Results: out of 346 articles submitted, 51 (14.7%) were published. Fourteen (11.9%) of the 118 studies on repeated TOS were published vs. 37 (16.2%) of the rest of the TOS (p: 0.4). The articles on repeated TOS neither included more patients nor involved a higher number of centers. Thirteen repeated TOS with at least three similar studies, but no published articles were identified. Conclusions: only a few articles on RA were published. One third of the studies submitted to the ACOR are repeated TOS, a fact that does not improve the publication rate.

Consecuencias de la artritis reumatoide en la articulación temporomandibular y su manejo odontológico / Consequences of rheumatoid arthritis in the temporomandibular joint and its dental management

Introducción: la artritis reumatoide es parte del grupo de las enfermedades autoinmunes con incidencia considerable sobre la población. Se caracteriza por la afección de las articulaciones del cuerpo que la padece; en mayor frecuencia se encuentra afectada la articulación temporomandibular por el complejo articular que ésta presenta; entre los signos y síntomas que comúnmente podemos encontrar en pacientes con este tipo de enfermedad son los chasquidos o ruidos articulares, dolor orofacial, pérdida o imposibilidad del movimiento de la mandíbula y cambios anatómicos localizados en el área de la articulación temporomandibular. Objetivo: describir las consecuencias que desencadena la artritis reumatoide sobre la articulación temporomandibular y cómo es para el odontólogo el manejo de estos pacientes en consulta, evaluar los tratamientos para cada caso sobre un correcto diagnóstico. Material y métodos: se realizó una revisión bibliográfica de artículos recientes sobre el tema, utilizando buscadores como SciELO, Elsevier y PubMed, siendo 30 las fuentes seleccionadas con idiomas en inglés y español. Resultados: esta enfermedad autoinmune se caracteriza por afectar múltiples articulaciones del cuerpo humano simétrica y bilateralmente incluyendo la articulación temporomandibular (ATM), lo cual conlleva al riesgo de desarrollar trastornos temporomandibulares (TTM). Es importante conocer los métodos para realizar un correcto diagnóstico oportuno de la ATM del paciente con artritis reumatoide (AR) con la finalidad de ofrecer un tratamiento conservador. Conclusión: los trastornos temporomandibulares desencadenantes de la artritis reumatoide son afecciones que se deben considerar para el buen manejo del paciente con este padecimiento, comprender y respaldar un diagnóstico clínico es de vital importancia para dar al paciente un tratamiento adecuado dependiendo el grado de complejidad en la que cada individuo se encuentra; conocer el manejo adecuado y encaminar al paciente a una mejor calidad de vida es clave en la consulta odontológica del día a día (AU)

Introduction: rheumatoid arthritis is part of the group of autoimmune diseases with considerable incidence in the population. It is characterized by the affection of the joints of the body that suffers from it; most frequently the temporomandibular joint is affected due to the articular complex that it presents; among the signs and symptoms that we can commonly find in patients with this type of disease are joint clicks or noises, orofacial pain, loss or impossibility of jaw movement and anatomical changes located in the temporomandibular joint area. Objective: to describe the consequences that rheumatoid arthritis triggers on the temporomandibular joint and how it is for the dentist to manage these patients in consultation, to evaluate the treatments for each case on a correct diagnosis. Material and methods: a bibliographic review of recent articles on the subject was carried out, using search engines such as SciELO, Elsevier and PubMed, with 30 sources selected in English and Spanish. Results: this autoimmune disease is characterized by affecting multiple joints of the human body symmetrical and bilaterally including the TMJ which leads to the risk of developing TMD. It is important to know the methods to make a correct diagnosis of the TMJ of the patient with RA in order to offer a conservative treatment. Conclusions: the temporomandibular disorders that trigger rheumatoid arthritis are conditions that should be considered for the proper management of the patient with this condition, understanding and supporting a clinical diagnosis is of vital importance to give the patient an adequate treatment depending on the degree of complexity in which each individual is; knowing the proper management and directing the patient to a better quality of life is key in the day-to-day dental practice (AU)

Hipogamaglobulinemia e rituximabe: relato de casos / Hypogammaglobulinemia and rituximab: case reports

Secondary immunodeficiency can result from neoplasms, infections, or immunosuppressive therapy. Rituximab (RTX) is an anti-CD20 antibody that depletes B lymphocytes and can induce symptomatic hypogammaglobulinemia. We report 3 cases of symptomatic hypogammaglobulinemia associated with the use of RTX. In patient 1 with rheumatoid arthritis, RTX induced low levels of immunoglobulins and recurrent airway infections. RTX discontinuation led to a normalization of the humoral immune response. Patients 2 and 3, treated with RTX for non-Hodgkin lymphoma and systemic lupus erythematosus, respectively, developed persistent secondary hypogammaglobulinemia requiring immunoglobulin replacement therapy for years. After RTX discontinuation, patients may experience rapid recovery of humoral function or remain with low serum immunoglobulin levels for extended periods. With the increasing use of therapies targeting components of the immune system, a high degree of clinical suspicion for the development of secondary immunodeficiency may minimize the morbidity and mortality associated with these therapies.

As imunodeficiências secundárias podem ser uma consequência de neoplasias, infecções ou tratamentos imunossupressores. O rituximabe (RTX) é um anticorpo anti-CD20 que depleta os linfócitos B e pode induzir uma hipogamaglobulinemia sintomática. Aqui, relatamos três casos de hipogamaglobulinemia sintomática associada ao uso de RTX. Na primeira paciente com artrite reumatoide, o RTX induziu a baixos níveis de imunoglobulinas associadas a infecções de vias aéreas de repetição. Após a suspensão do RTX, houve normalização da resposta imune humoral. Os outros dois casos, com o uso de RTX para tratamento de linfoma não-Hodgkin e lúpus eritematoso sistêmico, respectivamente, as pacientes evoluíram com hipogamaglobulinemia secundária persistente, com necessidade de reposição de imunoglobulina por vários anos. Pacientes tratados com RTX podem apresentar, após a sua suspensão, uma recuperação rápida da função humoral ou permanecerem com baixos níveis séricos de imunoglobulinas por longos períodos. Com o crescente uso dos tratamentos direcionados para componentes do sistema imunológico, um alto grau de suspeição clínica para o aparecimento de imunodeficiências secundárias pode minimizar a morbimortalidade associada a estes tratamentos.

Higher pain intensity is associated with less resilience in patients with rheumatoid arthritis / Maior intensidade de dor está associada com menor resiliência em pacientes com artrite reumatoide

ABSTRACT BACKGROUND AND OBJECTIVES: Rheumatoid arthritis is an inflammatory, chronic and autoimmune disease that causes joint damage and can lead to physical disability. Patients with chronic and debilitating diseases such as arthritis need to adapt to the new reality. These changes may have less impact on patients with greater self-efficacy and resilience. Psychosocial factors influence the quality of life (QoL) of these patients, so the aim of this study was to assess resilience in this population and its relationship with pain, functional capacity and disease activity. METHODS: This is a cross-sectional study carried out with patients at a medical specialties clinic, using a sociodemographic, a clinical-laboratory, a health assessment, a disease activity score questionnaires and the Wagnild and Young Resilience Scale. The data was analyzed using Fisher's Exact, Chi-square, Student's t and ANOVA tests. RESULTS: 120 patients participated in the study, 89.2% female, mean age 56.9 ± 10.7 years. Pain was classified as severe by 40.8%, 65.8% had disease in remission and 50.8% had mild disability. The resilience of 49.2% was high. There was an association between lower resilience and: presence of painful joints (p=0.004) and greater pain intensity (p=0.014). There was a lower average of resilience (130.95) in participants with severe disability. CONCLUSION: Patients with less resilient rheumatoid arthritis had greater functional disability, painful joints and greater pain intensity. In addition, from the moment additional measures are adopted, such as educational actions and behavioral strategies, with an emphasis on resilience, which help in the control and clinical outcome of the disease, there will certainly be a positive impact on the quality of life of these patients.

RESUMO JUSTIFICATIVA E OBJETIVOS: A artrite reumatoide é uma doença inflamatória, crônica e autoimune, que acarreta lesão articular e pode ocasionar incapacidade física. Pacientes com doenças crônicas e debilitantes como a artrite necessitam se adaptar à nova realidade. Essas mudanças podem ser menos impactantes em pacientes com maior autoeficácia e resiliência. Os fatores psicossociais exercem influência na qualidade de vida (QV) desses pacientes, portanto o objetivo deste estudo foi avaliar a resiliência nessa população e sua relação com dor, capacidade funcional e atividade da doença. MÉTODOS: Trata-se de uma pesquisa transversal, realizada com pacientes de uma clínica de especialidades médicas, através dos questionários sociodemográfico, clínico-laboratorial, de avaliação da saúde, de escore da atividade da doença,e avaliação da saúde, de escore da atividade da doença, e da escala de Resiliência de Wagnild e Young. A análise dos dados foi feita através dos testes Exato de Fisher, Qui-quadrado, t de Student e ANOVA. RESULTADOS: Participaram do estudo 120 pacientes, sendo 89,2% do sexo feminino, com média de idade de 56,9±10,7 anos. A dor foi classificada como intensa por 40,8%; 65,8% dos pacientes estavam com doença em remissão e 50,8% com incapacidade leve. A resiliência de 49,2% foi elevada. Foi verificada uma associação entre menor resiliência e: presença de articulações dolorosas (p=0,004) e maior intensidade de dor (p=0,014). Foi verificada menor média de resiliência (130,95) nos participantes com incapacidade grave. CONCLUSÃO: Pacientes com artrite reumatoide menos resilientes apresentaram maior incapacidade funcional, articulações dolorosas e maior intensidade de dor. Além disso, a partir do momento em que se adota medidas adicionais, tais como ações educativas e estratégias comportamentais, com ênfase na resiliência, que auxiliem no controle e no desfecho clínico da doença, certamente haverá impacto positivo na QV dos pacientes.

Recurrent acute coronary syndrome after infliximab infusion in a patient with rheumatoid arthritis: Case report

Case description: A 61-year-old male patient with uncontrolled rheumatoid arthritis presented acute coronary syndrome on three occasions, less than 48 hours after infliximab infusion. Clinical findings: He presented with ST-elevation myocardial infarction on two occasions and non-ST-elevation acute coronary syndrome on one, with the identification of multivessel coronary disease. Treatment and outcome: Coronary intervention was performed with thrombus aspiration, medicated stent implantation, medicated balloon angioplasty, discontinuation of infliximab, and modification and optimization of cardiovascular pharmacological management. Clinical relevance: Patients with rheumatoid arthritis have subclinical cardiovascular disease and increased cardiovascular risk. The evidence regarding the relationship between infliximab and ischemic heart disease is controversial. A wide clinical spectrum of cardiac involvement with infliximab infusion is found in case reports, ranging from stable angina to ST-segment elevation acute coronary syndrome. The pathophysiology is not elucidated, with hypotheses proposing plaque rupture, allergic reactions, and vasoconstriction as possible disease mechanisms. The direct association between infliximab infusion and acute coronary syndrome needs more clinical research to optimize the management and prognosis of patients presenting with this type of complication.

Descripción del caso: Paciente masculino de 61 años con artritis reumatoide no controlada, en manejo con infliximab, quién presentó en tres oportunidades síndrome coronario agudo menos de 48 horas posterior a la aplicación del medicamento. Hallazgos clínicos: Presentó infarto con elevación del ST en dos ocasiones y síndrome coronario agudo sin elevación del ST en una oportunidad, encontrándose enfermedad coronaria multivaso. Tratamiento y resultado: Se realizó intervención coronaria con tromboaspiración, implante de stents medicados y angioplastia con balón medicado, suspensión del infliximab y modificación y optimización de manejo farmacológico cardiovascular. Relevancia clínica: Los pacientes con artritis reumatoide tienen enfermedad cardiovascular subclínica y mayor riesgo cardiovascular. La evidencia respecto a la relación entre infliximab y cardiopatía isquémica es controversial. En reportes de caso se encuentra un amplio espectro clínico de compromiso cardíaco con la infusión de infliximab, que va desde la angina estable hasta el síndrome coronario agudo con elevación del segmento ST. La fisiopatología no está claramente dilucidada, con hipótesis que proponen la ruptura de placa, reacciones alérgicas y la vasoconstricción como posibles mecanismos de enfermedad. La asociación directa entre la infusión de infliximab y el síndrome coronario agudo necesita más investigación clínica con el fin de optimizar el manejo y pronóstico de los pacientes que presentan este tipo de complicaciones.

Medicamentos para artrite reumatoide fornecidos pelo Sistema Único de Saúde em 2019 no Brasil: estudo de coorte / Drugs for rheumatoid arthritis provided by the Unified Health System in 2019 in Brazil: a cohort study

Resumo Este artigo tem como objetivo analisar características do fornecimento e fatores associados ao tratamento da artrite reumatoide no Brasil, com foco nos medicamentos biológicos modificadores do curso da doença (MMCDbio). Foi realizado um estudo retrospectivo com dados secundários do Sistema de Informação Ambulatorial do Sistema Único de Saúde. Foram incluídos pacientes com 16 anos ou mais, atendidos nos doze meses do ano de 2019. As análises foram feitas com fatores de exposição em relação aos desfechos: uso de MMCDbio e porte populacional. O estudo incluiu 155.679 pacientes, sendo 84,6% mulheres. Observou-se maior troca de MMCDbio e maior provisão de médicos reumatologistas nos municípios de maior porte (mais de 500 mil habitantes). Quase 40% dos pacientes utilizaram MMCDbio e estes apresentaram maior adesão ao tratamento (57,0% versus 64%, p=0,001). A dispensação de MMCDbio ocorreu para mais de um terço dos pacientes tratados para AR no Brasil e esteve associada ao maior percentual de disponibilidade de médicos reumatologistas e ao maior porte populacional dos municípios.

Abstract This study analyzes supply characteristics and factors associated with the treatment of rheumatoid arthritis in Brazil, with a focus on disease course-modifying biological drugs (bioDMARDs). A retrospective study was conducted with secondary data from the Outpatient Information System of the Unified Health System. Patients aged 16 years or older who were treated in 2019 were eligible. The analyses were performed with exposure factors in relation to the outcomes: bioDMARD use and population size. The study included 155,679 patients, 84.6% of whom were women. There was a greater exchange of bioDMARDs and a greater supply of rheumatologists in the larger municipalities (more than 500,000 inhabitants). Almost 40% of the patients used bioDMARDs, and they showed greater adherence to treatment (57.0% versus 64%, p=0.001). The dispensing of bioDMARDs occurred in more than one-third of the patients treated for rheumatoid arthritis (RA) in Brazil and was associated with a higher percentage of availability of rheumatologists and larger population size.

A rat model of rheumatoid arthritis: TDZD-8 is associated with the protection against the induction of the synovium knee joint IL-17A/GSK3beta/ROS/alpha-SMA axis of fibrosis / Un modelo de rata de artritis reumatoide: TDZD-8 está asociado con la protección contra la inducción del eje de fibrosis de la articulación sinovial de la rodilla IL-17A/GSK3ß/ROS/α-SMA

SUMMARY: Rheumatoid arthritis (RA) that affects the synovial knee joint causes swelling of the synovial membrane and tissue damage. Interleukin-17A (IL-17A) and the enzyme glycogen synthase kinase-3β (GSK3β) are involved in the pathogenesis of RA. The link between IL-17A, GSK3β, the oxidative stress, and the profibrogenic marker alpha-smooth muscle actin (α-SMA) with and without TDZD-8, GSK3β inhibitor has not been studied before. Consequently, active immunization of rats was performed to induce RA after three weeks using collagen type II (COII) injections. The treated group received daily injection of 1 mg/kg TDZD-8 for 21 days following the immunization protocol (COII+TDZD-8). Blood and synovium tissue samples were harvested at the end of the experiment. RA development was confirmed as corroborated by a substantial increase in blood levels of the highly specific autoantibody for RA, anti-citrullinated protein antibody as well as augmentation of reactive oxidative species (ROS) levels measured as lipid peroxidation. RA induction also increased synovium tissue levels of IL-17A and the profibrogenic marker, α-SMA. All these parameters seemed to be significantly (p<0.0001) ameliorated by TDZD-8. Additionally, a significant correlation between IL-17A, ROS, and α-SMA and biomarkers of RA was observed. Thus, knee joint synovium RA induction augmented IL-17A/GSK3β/ROS/α-SMA axis mediated arthritis in a rat model of RA, which was inhibited by TDZD-8.

La artritis reumatoide (AR) que afecta la articulación sinovial de la rodilla provoca inflamación de la membrana sinovial y daño tisular. La interleucina-17A (IL-17A) y la enzima glucógeno sintasa quinasa-3β (GSK3β) están involucradas en la patogenia de la AR. No se ha estudiadol vínculo entre IL-17A, GSK3β, el estrés oxidativo y el marcador profibrogénico actina de músculo liso alfa (α-SMA) con y sin inhibidor de TDZD-8, GSK3β. En consecuencia, se realizó una inmunización activa de ratas para inducir la AR después de tres semanas usando inyecciones de colágeno tipo II (COII). El grupo tratado recibió una inyección diaria de 1 µg/ kg de TDZD-8 durante 21 días siguiendo el protocolo de inmunización (COII+TDZD-8). Se recogieron muestras de sangre y tejido sinovial al final del experimento. El desarrollo de AR se confirmó como lo corroboró el aumento sustancial en los niveles sanguíneos del autoanticuerpo altamente específico para AR, el anticuerpo antiproteína citrulinada, así como el aumento de los niveles de especies oxidativas reactivas (ROS) medidos como peroxidación lipídica. La inducción de AR también aumentó los niveles de tejido sinovial de IL-17A y el marcador profibrogénico, α-SMA. Todos estos parámetros parecían mejorar significativamente (p<0,0001) con TDZD-8. Además, se observó una correlación significativa entre IL- 17A, ROS y α-SMA y biomarcadores de AR. Por lo tanto, la inducción de AR en la sinovial de la articulación de la rodilla aumentó la artritis mediada por el eje IL-17A/GSK3β/ROS/α-SMA en un modelo de rata de AR, que fue inhibida por TDZD-8.

Efecto de la epigenética en la artritis reumatoide / Effect of epigenetics on rheumatoid arthritis

La artritis reumatoide es una enfermedad autoinmune e inflamatoria que afecta de manera predominante a las articulaciones diartrodiales. En esta patología los factores ambientales o conductuales pueden actuar en sinergia con la predisposición genética, acelerando el inicio y la gravedad de la enfermedad. Este vínculo entre el medio ambiente y el genoma está mediado por marcas epigenéticas en el ácido desoxirribonucleico, incluyendo su metilación, la modificación de histonas y la regulación mediada por ácido ribonucleico no codificante. La epigenética puede generar cambios fenotípicos hereditarios, que no están determinados por modificaciones en la secuencia del ácido desoxirribonucleico y, en consecuencia, son reversibles. Por lo tanto la dieta, los medicamentos y otros factores ambientales, tendrían la capacidad de modularlos. La identificación de una desregulación epigenética específica, puede ofrecer una mayor comprensión de la fisiopatología de la enfermedad e influenciar positivamente en la prevención, diagnóstico y desarrollo de nuevas dianas terapéuticas.

Rheumatoid arthritis is an autoimmune and inflammatory disease that predominantly affects the diarthrodial joints. In this pathology, environmental or behavioral factors can act in synergy with genetic predisposition, accelerating the onset and severity of the disease. This link between the environment and the genome is mediated by epigenetic marks on deoxyribonucleic acid, including its methylation, histone modification, and noncoding ribonucleic acid-mediated regulation. Epigenetics can generate heritable phenotypic changes, which are not determined by modifications in the deoxyribonucleic acid sequence and are therefore reversible. Therefore, diet, medications and other environmental factors would have the ability to modulate them. The identification of a specific epigenetic dysregulation can offer a better understanding of the pathophysiology of the disease and positively influence the prevention, diagnosis and development of new therapeutic targets.

Ansiedad, depresión y vulnerabilidad al estrés en personas con diagnóstico de artritis reumatoidea: un estudio exploratorio del Hospital de Clínicas de la Universidad Nacional de Asunción / Anxiety, depression, and vulnerability to stress in people diagnosed with rheumatoid arthritis: An exploratory study at the Hospital de Clínicas of the Universidad Nacional de Asunción

Antecedentes: Estudios observacionales han descrito una alta prevalencia de depresión y ansiedad en la artritis reumatoidea: los trastornos depresivos mayores se detectan en el 17 % de los pacientes con la patología, y la inflamación local y sistémica desempeña un papel importante en la ansiedad y la depresión. Objetivos: El objetivo general de esta investigación fue determinar la frecuencia de ansiedad, depresión y vulnerabilidad al estrés en pacientes con diagnóstico de artritis reumatoidea. Materiales y métodos: Este fue un estudio observacional, descriptivo de asociación cruzada y temporalmente prospectivo. El muestreo fue no probabilístico de casos consecutivos. Se incluyó a personas adultas con diagnóstico de artritis reumatoide que consultaron en el Departamento de Reumatología del Hospital de Clínicas, entre agosto y octubre del 2022. Para el diagnóstico psiquiátrico se utilizaron los siguientes instrumentos: Escala de Ansiedad Generalizada (GAD-7), Patient Health Questionnaire (PHQ-2) y Escala de Vulnerabilidad al Estrés de Smith y Miller. Resultados: Se incluyó a 36 pacientes, todas mujeres, con edades comprendidas entre los 20 y 77 años. El 27,8 % tenía depresión, según los puntos de corte del PHQ-2. El 22,2 % presentaba ansiedad, según los puntos de corte de GAD-7. En cuanto al estrés, el 22,2 % tenía vulnerabilidad a este y el 5,6 % era seriamente vulnerable. Conclusión: Depresión, ansiedad y vulnerabilidad al estrés son comorbilidades frecuentemente observadas en pacientes con artritis reumatoidea. Se requieren de intervenciones específicas de salud mental para abordar estas cuestiones y mejorar la calidad de vida de los pacientes afectados.

Background: Observational studies have described a high prevalence of depression and anxiety in rheumatoid arthritis: major depressive disorders are detected in 17 % of patients with the pathology, and local and systemic inflammation play an important role in anxiety and depression. Objectives: The overall objective of this research was to determine the frequency of anxiety, depression, and vulnerability to stress in patients diagnosed with rheumatoid arthritis. Materials and methods: This was an observational, descriptive, temporally prospective, cross-association study. Sampling was non-probabilistic of consecutive cases. We included adults with a diagnosis of rheumatoid arthritis who consulted at the Rheumatology Department of the Hospital de Clínicas between August and October 2022. The following instruments were used for psychiatric diagnosis: Generalized Anxiety Scale (GAD-7), Patient Health Questionnaire (PHQ-2) and Smith and Miller's Stress Vulnerability Scale. Results: Thirty-six patients, all women, aged between 20 and 77 years, were included in the study. The 27.8 % had depression, according to the cut-off points of the PHQ-2. Anxiety was present in 22.2 %, according to the GAD-7 cut-off points. Regarding stress, 22.2 % were vulnerable to stress and 5.6 % were seriously vulnerable. Conclusion: Depression, anxiety and vulnerability to stress are frequently observed comorbidities in patients with rheumatoid arthritis. Specific mental health interventions are required to address these issues and improve the quality of life of affected patients.

A Rat Model of Rheumatoid Arthritis: TDZD-8 is Associated with the Protection Against the Induction of the Synovium Knee Joint IL-17A/GSK3β/ROS/α-SMA Axis of Fibrosis

SUMMARY: Rheumatoid arthritis (RA) that affects the synovial knee joint causes swelling of the synovial membrane and tissue damage. Interleukin-17A (IL-17A) and the enzyme glycogen synthase kinase-3β (GSK3β) are involved in the pathogenesis of RA. The link between IL-17A, GSK3β, the oxidative stress, and the profibrogenic marker alpha-smooth muscle actin (α-SMA) with and without TDZD-8, GSK3β inhibitor has not been studied before. Consequently, active immunization of rats was performed to induce RA after three weeks using collagen type II (COII) injections. The treated group received daily injection of 1 mg/kg TDZD-8 for 21 days following the immunization protocol (COII+TDZD-8). Blood and synovium tissue samples were harvested at the end of the experiment. RA development was confirmed as corroborated by a substantial increase in blood levels of the highly specific autoantibody for RA, anti-citrullinated protein antibody as well as augmentation of reactive oxidative species (ROS) levels measured as lipid peroxidation. RA induction also increased synovium tissue levels of IL-17A and the profibrogenic marker, α-SMA. All these parameters seemed to be significantly (p<0.0001) ameliorated by TDZD-8. Additionally, a significant correlation between IL-17A, ROS, and α-SMA and biomarkers of RA was observed. Thus, knee joint synovium RA induction augmented IL-17A/GSK3β/ROS/α-SMA axis mediated arthritis in a rat model of RA, which was inhibited by TDZD-8.

La artritis reumatoide (AR) que afecta la articulación sinovial de la rodilla provoca inflamación de la membrana sinovial y daño tisular. La interleucina-17A (IL-17A) y la enzima glucógeno sintasa quinasa-3β (GSK3β) están involucradas en la patogenia de la AR. No se ha estudiadol vínculo entre IL-17A, GSK3β, el estrés oxidativo y el marcador profibrogénico actina de músculo liso alfa (α-SMA) con y sin inhibidor de TDZD-8, GSK3β. En consecuencia, se realizó una inmunización activa de ratas para inducir la AR después de tres semanas usando inyecciones de colágeno tipo II (COII). El grupo tratado recibió una inyección diaria de 1 µg/ kg de TDZD-8 durante 21 días siguiendo el protocolo de inmunización (COII+TDZD-8). Se recogieron muestras de sangre y tejido sinovial al final del experimento. El desarrollo de AR se confirmó como lo corroboró el aumento sustancial en los niveles sanguíneos del autoanticuerpo altamente específico para AR, el anticuerpo antiproteína citrulinada, así como el aumento de los niveles de especies oxidativas reactivas (ROS) medidos como peroxidación lipídica. La inducción de AR también aumentó los niveles de tejido sinovial de IL-17A y el marcador profibrogénico, α-SMA. Todos estos parámetros parecían mejorar significativamente (p<0,0001) con TDZD-8. Además, se observó una correlación significativa entre IL- 17A, ROS y α-SMA y biomarcadores de AR. Por lo tanto, la inducción de AR en la sinovial de la articulación de la rodilla aumentó la artritis mediada por el eje IL-17A/GSK3β/ROS/α-SMA en un modelo de rata de AR, que fue inhibida por TDZD-8.

Clinician's dilemma: Naproxen-induced liver injury

Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID) in pediatric population, used for mild-to-moderate pains, arthritis, and other immune-mediated disorders. It rarely causes clinically apparent liver injury in the adult population taking high doses of the drug over a prolonged period and is reported even rarer in pediatric population. We present a case of drug-induced liver injury (DILI) in a 13-year-old girl taking naproxen in therapeutic doses for juvenile rheumatoid arthritis. There was a complete recovery of liver function following discontinuation of naproxen therapy.

Effect of Sodhananga Achasnehapana Followed by Virechana in the Management of Rheumatoid Arthritis: A Case Report

Rheumatoid arthritis is a chronic, progressive autoimmune arthropathy and characterized by bilateral symmetrical involvement of joints with some systemic clinical features. Treatment in allopathic medicine involves NSAIDS and steroids, which carry their own collateral burden of side effects in long term use. According to clinical features, described in Ayurveda, Vatarakta closely resembles with Rheumatoid arthritis. The study is done to find the effect of Sodhananga Achasnehapana with Guggutiktaka ghritha followed by Virechana with Nimbamrita eranda taila in Rheumatoid Arthritis. Methods: It is a simple random single case study done at Government Ayurveda College Panchakarma Hospital, Poojappura, Thiruvananthapuram. Here a case of Vatarakta (Vatakapahadikam) was treated with Sodhananga Achasnehapana with Guggutiktaka ghritha followed by Virechana with Nimbamrita eranda taila after Rukshana karma. Results: The treatment was effective in reducing the ESR, RA factor and CRP levels of the patient diagnosed with Rheumatoid arthritis. Conclusion: The case report shows that Ayurvedic treatment is potent and effective in the management of Rheumatoid arthritis. There was no adverse effect found in the treatment. Hence it can be concluded that RA can be effectively and safely treated by using the Chikitsa siddhanta mentioned in Ayurveda

Rituximab, a Safer Option for Rheumatoid Arthritis: A Comparison of the Reported Adverse Events of Approved Monoclonal Antibodies

Monoclonal antibodies (mAbs), which are commonly used to treat rheumatoid arthritis (RA), have been linked to a variety of adverse events (AEs). The objective of the study was to compare the safety profiles of six FDA approved mAbs (sarilumab, tocilizumab, adalimumab, golimumab, infliximab, and rituximab) marketed for the treatment of RA. A systematic review of the literature was conducted using the databases PubMed, Cochrane Library, and Science Direct. The manuscript comprised a total of 23 clinical studies. The percentage of patients who had AEs was calculated and presented using box-whisker and forest plots. Infections and infestations were found to be the most common AEs in RA patients treated with mAbs. Raised alanine aminotransferase (ALT), aspartate aminotransferase (AST), upper respiratory tract infection (URTI), and nasopharyngitis were frequently reported. The most common AEs were reported with adalimumab. The highest percentage of patients reporting AEs was associated with golimumab (52%), while rituximab had the fewest AEs (4.9%). In conclusion, rituximab appears to be a safer treatment option for RA as it is found to be associated with a lower risk of AEs, particularly respiratory infections.

A stitch in time saves my (ne) (vision)

Background: Corneal melt with iris prolapse is a rare complication of autoimmune diseases, especially rheumatoid arthritis. Purpose: To highlight a challenging case of a peripheral ulcerative keratitis (PUK) with corneal melt and iris prolapse in a patient’s only eye. Synopsis: A 56?year?old Asian Indian male presented with blurring of vision in the right eye and was diagnosed with cataract. He was a known type 2 diabetes mellitus and a rheumatoid arthritis patient and was not on treatment. He had been previously diagnosed with PUK in the left eye and was lost to follow?up due to coronavirus disease 2019 (COVID?19) after therapeutic penetrating keratoplasty and lost his vision in that eye. Cataract surgery in the right eye was done under cover of immunosuppression. Subsequently, he developed PUK and was treated with a glue and bandage contact lens. Again, he was lost to follow?up and then presented a few months later with corneal melt with iris prolapse in the right eye. We describe in the video the surgical and medical challenges and successful salvage of both the eyeball and the vision. Highlights: Highlights include the following: 1. A rare case of corneal melt with iris prolapse. 2. Demonstration of surgical technique of patch graft. 3. Anterior segment optical coherence tomography before and after the procedure.