Tofacitinib treatment of rheumatoid arthritis increases senescent T cell frequency in patients and limits T cell function in vitro.

Unraveling the immune signatures in rheumatoid arthritis (RA) patients receiving various treatment regimens can aid in comprehending the immune mechanisms' role in treatment efficacy and side effects. Given the critical role of cellular immunity in RA pathogenesis, we sought to identify T-cell profiles characterizing RA patients under specific treatments. We compared 75 immunophenotypic and biochemical variables in healthy donors (HD) and RA patients, including those receiving different treatments as well as treatment-free patients. Additionally, we conducted in vitro experiments to evaluate the direct effect of tofacitinib on purified naïve and memory CD4+ and CD8+ T cells. Multivariate analysis revealed that tofacitinib-treated patients segregated from HD at the expense of T-cell activation, differentiation, and effector function-related variables. Additionally, tofacitinib led to an accumulation of peripheral senescent memory CD4+ and CD8+ T cells. In vitro, tofacitinib impaired the activation, proliferation, and effector molecules expression and triggered senescence pathways in T-cell subsets upon TCR-engagement, with the most significant impact on memory CD8+ T cells. Our findings suggest that tofacitinib may activate immunosenescence pathways while simultaneously inhibiting effector functions in T cells, both effects likely contributing to the high clinical success and reported side effects of this JAK inhibitor in RA.

Dynamics of circulating follicular helper T cell subsets and follicular regulatory T cells in rheumatoid arthritis patients according to HLA-DRB1 locus.

B cells, follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are part of a circuit that may play a role in the development or progression of rheumatoid arthritis (RA). With the aim of providing further insight into this topic, here we evaluated the frequency of different subsets of Tfh and Tfr in untreated and long-term treated RA patients from a cohort of Argentina, and their potential association with particular human leukocyte antigen (HLA) class-II variants and disease activity. We observed that the frequency of total Tfh cells as well as of particular Tfh subsets and Tfr cells were increased in seropositive untreated RA patients. Interestingly, when analyzing paired samples, the frequency of Tfh cells was reduced in synovial fluid compared to peripheral blood, while Tfr cells levels were similar in both biological fluids. After treatment, a decrease in the CCR7loPD1hi Tfh subset and an increase in the frequency of Tfr cells was observed in blood. In comparison to healthy donors, seropositive patients with moderate and high disease activity exhibited higher frequency of Tfh cells while seropositive patients with low disease activity presented higher Tfr cell frequency. Finally, we observed that HLA-DRB1*09 presence correlated with higher frequency of Tfh and Tfr cells, while HLA-DRB1*04 was associated with increased Tfr cell frequency. Together, our results increase our knowledge about the dynamics of Tfh and Tfr cell subsets in RA, showing that this is altered after treatment.

An Argentinean cohort of patients with rheumatic and immune-mediated diseases vaccinated for SARS-CoV-2: the SAR-CoVAC Registry-protocol and preliminary data.

BACKGROUND/OBJECTIVE: To evaluate the efficacy and safety of SARS-CoV-2 vaccine in patients with rheumatic and immune-mediated inflammatory diseases (IMIDs) in Argentina: the SAR-CoVAC registry. METHODS: SAR-CoVAC is a national, multicenter, and observational registry. Adult patients with rheumatic or IMIDs vaccinated for SARS-CoV-2 were consecutively included between June 1 and September 17, 2021. Sociodemographic data, comorbidities, underlying rheumatic or IMIDs, treatments received, their modification prior to vaccination, and history of SARS-CoV-2 infection were recorded. In addition, date and place of vaccination, type of vaccine applied, scheme, adverse events (AE), disease flares, and new immune-mediated manifestations related to the vaccine were analyzed. RESULTS: A total of 1234 patients were included, 79% were female, with a mean age of 57.8 (SD 14.1) years. The most frequent diseases were rheumatoid arthritis (41.2%), osteoarthritis (14.5%), psoriasis (12.7%), and spondyloarthritis (12.3%). Most of them were in remission (28.5%) or low disease activity (41.4%). At the time of vaccination, 21% were receiving glucocorticoid treatment, 35.7% methotrexate, 29.7% biological (b) disease modifying anti-rheumatic drugs (DMARD), and 5.4% JAK inhibitors. In total, 16.9% had SARS-CoV-2 infection before the first vaccine dose. Most patients (51.1%) received Gam-COVID-Vac as the first vaccine dose, followed by ChAdOx1 nCoV-19 (32.8%) and BBIBP-CorV (14.5%). Half of them (48.8%) were fully vaccinated with 2 doses; 12.5% received combined schemes, being the most frequent Gam-COVID-Vac/mRAN-1273. The median time between doses was 51 days (IQR 53). After the first dose, 25.9% of the patients reported at least one AE and 15.9% after the second, being flu-like syndrome and local hypersensitivity the most frequent manifestations. There was one case of anaphylaxis. Regarding efficacy, 63 events of SARS-CoV-2 infection were reported after vaccination, 19% occurred during the first 14 days post-vaccination, 57.1% after the first dose, and 23.8% after the second. Most cases (85.9%) were asymptomatic or mild and 2 died due to COVID-19. CONCLUSIONS: In this national cohort of patients, the most common vaccines used were Gam-COVID-Vac and ChAdOx1 nCoV-19. A quarter of the patients presented an AE and 5.1% presented SARS-CoV-2 infection after vaccination, in most cases mild. STUDY REGISTRATION: This study has been registered in ClinicalTrials.gov under the number: NCT04845997. Key Points • This study shows real-world data about efficacy and safety of SARS-CoV-2 vaccination in patients with rheumatic and immune-mediated inflammatory diseases. Interestingly, different types of vaccines were used including vector-based, mRNA, and inactivated vaccines, and mixed regimens were enabled. • A quarter of the patients presented an adverse event. The incidence of adverse events was significantly higher in those receiving mRAN-1273 and ChAdOx1 nCoV-19. • In this cohort, 5.1% presented SARS-CoV-2 infection after vaccination, in most cases mild.

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

Lupus eritematoso sistémico: datos sociodemográficos y su correlación clínico-analítica en un hospital universitario / Systemic Lupus Erythemathosus: sociodemographic data and clinical correlation at an university hospital

Objetivos: Analizar las características sociodemográficas y clínicas de los pacientes con Lupus Eritematoso Sistémico (LES) del Servicio de Reumatología de un Hospital Universitario de Córdoba. Pacientes y métodos: Estudio retrospectivo, descriptivo y analítico de 303 pacientes adultos con LES asistidos entre 1987-2017, que cumplían con los criterios ACR1982. Se registraron datos sociodemográficos, clínicos, de laboratorio, internaciones, óbitos y los tratamientos. Los datos fueron analizados con Excel, Infostat y SPSS 11.5 para Windows. Resultados: El 92% eran mujeres, 44% de ellas y 61% de los hombres eran mestizos. La edad promedio al diagnóstico fue de 32 años y el tiempo medio de evolución de la enfermedad de 11 años. Un tercio terminó la escuela primaria y la mayoría pertenecía al nivel socieconómico medio. Las manifestaciones del aparato locomotor y dermatológicas fueron las más frecuentes como presentación y evolución de la enfermedad. El 60% mostró compromiso renal, siendo la glomerulonefritis tipo 4 el hallazgo histopatológico prevalente. Las causas de óbito fueron septicemia y hemorragia alveolar principalmente, asociados a SLICC más alto, anti-DNA (+), leucopenia, nivel socioeconómico medio y bajo y raza mestiza como marcadores de mal pronóstico. Conclusiones: En esta serie predominaron sexo femenino, raza mestiza, nivel socioeconómico medio y nivel de instrucción primario. Los síntomas de presentación fueron osteoarticulares y dérmicos. Las causas de muerte fueron infecciones o hemorragia alveolar. Fueron factores de mal pronóstico: anti-DNA, leucopenia, etnia mestiza y bajo nivel socioeconómico

Objective: to analyze demographic and clinical characteristics in SLE patients from a university hospital in Córdoba. Patients and Methods: We analyzed retrospectively 303 adult SLE patients assisted between 1987 and 2017 who met ACR1982 SLE criteria. Demographic, clinical and laboratory data and causes of death, hospitalization and treatments were analyzed with excel, infostat and SPSS for Windows. Results: 92% were women (race: women 44% mestizo; men 61% mestizo; mean age at diagnosis: 32 years, mean time of evolution 11 years). 1/3 of them finished primary school and most of them had medium socioeconomic status. Musculoskeletal and skin involvement was most frequent as presentation symptom and during the evolution of disease. 60% had renal involvement being type 4 glomerulonephritis the most prevalent histopathological finding. Causes of death were septicemia and alveolar hemorrhage, associated with higher SLICC, anti-DNA (+), leucopenia, low socioeconomic status and mestizo race as markers of poor prognosis. Conclusion: Female gender, mestizo race, medium socioeconomic status and primary level of education predominated in this series. Presentation symptoms were musculoskeletal and skin involvement. Causes of death were infections or alveolar hemorrhage. Anti-DNA (+), leucopenia, low socioeconomic status and mestizo race were markers of poor prognosis

PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment.

Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24hiCD38hi B cells decreased. CD19+ B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8+ T cell proliferation and cytokine production in a PD-L1-dependent manner. Conclusions: Our results show that PD-L1+ B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1+ B cells could thus provide new perspectives for future treatment strategies.

Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis.

OBJECTIVE: Inhibitory receptors are essential for the regulation of effector immune responses and may play critical roles in autoimmune diseases. We evaluated whether inhibitory receptor expression on T cells from patients with rheumatoid arthritis (RA) were correlated with immune activation, disease activity, and response to treatment, as well as whether inhibitory receptor-mediated pathways were functional. METHODS: Using flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from the blood and synovial fluid (SF) of RA patients ex vivo and after culture. The relationship of each parameter with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and response to treatment was examined. RESULTS: In RA patients with low levels of T cell activation, inhibitory receptor expression showed an inverse relationship with the DAS28-ESR. The frequency of T cells expressing multiple inhibitory receptors was reduced in untreated RA patients but returned to normal levels in treated patients. RA patients who responded to treatment showed an augmented frequency of inhibitory receptor-expressing T cells that correlated with reduced inflammatory cytokine production in comparison to nonresponders. Higher frequencies of effector and memory T cells that expressed multiple inhibitory receptors were seen in SF than in peripheral blood. Notably, inhibitory pathways were operative in blood and synovial T cells from all RA patients, although cells from nonresponder patients were less sensitive to inhibition. CONCLUSION: Inhibitory receptor expression on T cells from RA patients is inversely correlated with effector T cell function and disease activity and may predict response to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatment strategies to regulate acute local inflammation.

Células T helper foliculares en sangre periférica de pacientes con artritis reumatoide / Follicular helper T cells in peripheral blood of patients with rheumatoid arthritis

Introducción. La artritis reumatoidea (AR) es una enfermedad autoinmune y crónica caracterizada por la presencia de autoanticuerpos como factor reumatoide (FR) y anticuerpos antiproteínas citrulinadas. Una población de células T helper foliculares (Tfh), que expresan CD4+CXCR5+, colabora con las células B para la producción de anticuerpos. La expresión diferencial de CXCR3 y CCR6 dentro de las células CD4+CXCR5+ define 3 subpoblaciones mayores: CXCR3+CCR6− (Tfh1), CXCR3-CCR6− (Tfh2) y CXCR3-CCR6+ (Tfh17). El objetivo del estudio fue evaluar si existe asociación entre el porcentaje de estas células y la AR, y la correlación de las mismas con actividad de la enfermedad. Material y métodos. Participaron 24 pacientes con AR, 22 controles saludables (CS) y 16 pacientes con artritis indiferenciada (AI). Los porcentajes de las células CD4+CXCR5+ y sus subpoblaciones fueron analizados por citometría de flujo. Resultados. No hubo diferencias en los porcentajes de células CD4+CXCR5+ entre los pacientes con AR y CS o entre AR y AI. Tampoco en las subpoblaciones Tfh1, Tfh2 y Tfh17. No hubo correlación entre las células T CD4+CXCR5+, Tfh1, Tfh2 y Tfh17 y el «Disease Activity Score in twenty-eigth joints» (DAS28), así como tampoco con la velocidad de sedimentación globular. Sorpresivamente, hubo una correlación positiva entre las células Tfh17 y la proteína C reactiva. Finalmente, no hubo correlación entre las células TCD4+CXCR5+ o cualquiera de las subpoblaciones y antivimentina mutada citrulinada así como tampoco entre dichas células y el FR. Conclusión. No se hallaron diferencias entre los porcentajes de las células T CD4+CXCR5+ y sus subpoblaciones en sangre periférica de los pacientes con AR y las células de los grupos controles. Esto no descarta un papel patogénico de estas células en el desarrollo y actividad de la AR (AU)

Introduction. Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by the presence of different autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies. CD4T cells expressing CXCR5, referred as follicular helper T cells (Tfh), collaborate with B cells to produce antibodies. Differential expression of CXCR3 and CCR6 within CD4+CXCR5+ T cells defines three mayor subsets: CXCR3+CCR6− (Tfh1), CXCR3-CCR6− (Tfh2) and CXCR3-CCR6+ (Tfh17). The aim of the study was to assess whether there is an association between the percentage of these cells and RA and whether there is a correlation with disease activity. Material and methods. Twenty-four RA patients, 22 healthy controls (HC) and 16 undifferentiated arthritis (UA) patients were included. Percentage of CD4+CXCR5+ T cells and their subsets were analyzed by flow cytometry. Results. No differences were found in the percentages of CD4+CXCR5+ T cells in the comparison of RA vs HC or RA vs UA patients. Tfh1, Tfh2 and Tfh17 subsets showed no differences either. There was no correlation between CD4+CXCR5+T cells, Tfh1, Tfh2 and Tfh17, and Disease Activity Score in twenty-eight joints (DAS28) or erythrocyte sedimentation rate. Surprisingly, there was a positive correlation between Tfh17 cells and C-reactive protein. Finally, there was no correlation between CD4+CXCR5+ T cells, or their subsets, and anti-mutated citrullinated vimentin, or between the cells and RF. Conclusion. There were no differences between the percentages of CD4+CXCR5+ T cells and their subsets in peripheral blood of RA patients and the percentages of cells in the control groups. This finding does not rule out a pathogenic role of these cells in the development and activity of RA (AU)

Follicular helper T cells in peripheral blood of patients with rheumatoid arthritis. / Células T helper foliculares en sangre periférica de pacientes con artritis reumatoide.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by the presence of different autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies. CD4T cells expressing CXCR5, referred as follicular helper T cells (Tfh), collaborate with B cells to produce antibodies. Differential expression of CXCR3 and CCR6 within CD4+CXCR5+ T cells defines three mayor subsets: CXCR3+CCR6- (Tfh1), CXCR3-CCR6- (Tfh2) and CXCR3-CCR6+ (Tfh17). The aim of the study was to assess whether there is an association between the percentage of these cells and RA and whether there is a correlation with disease activity. MATERIAL AND METHODS: Twenty-four RA patients, 22 healthy controls (HC) and 16 undifferentiated arthritis (UA) patients were included. Percentage of CD4+CXCR5+ T cells and their subsets were analyzed by flow cytometry. RESULTS: No differences were found in the percentages of CD4+CXCR5+ T cells in the comparison of RA vs HC or RA vs UA patients. Tfh1, Tfh2 and Tfh17 subsets showed no differences either. There was no correlation between CD4+CXCR5+T cells, Tfh1, Tfh2 and Tfh17, and Disease Activity Score in twenty-eight joints (DAS28) or erythrocyte sedimentation rate. Surprisingly, there was a positive correlation between Tfh17 cells and C-reactive protein. Finally, there was no correlation between CD4+CXCR5+ T cells, or their subsets, and anti-mutated citrullinated vimentin, or between the cells and RF. CONCLUSION: There were no differences between the percentages of CD4+CXCR5+ T cells and their subsets in peripheral blood of RA patients and the percentages of cells in the control groups. This finding does not rule out a pathogenic role of these cells in the development and activity of RA.

Linfoma T cutáneo en paciente con artritis reumatoidea / Cutaneous T cel lymphoma in a patient with rheumatoid arthritis

La artritis reumatoidea incrementa el riesgo de muerte en pacientes que la padecen, ya sea por las comorbilidades como enfermedades cardiovasculares y las infecciones, como así también por una mayor frecuencia de desórdenes linfoproliferativos asociados a la enfermedad de base. Se presenta el caso de un paciente de sexo masculino de 74 años de edad, con artritis reumatoidea poliarticular y nodular de larga data. Tratado con DMARs, etanercept y abatacept con poca eficacia, por lo que inició rituximab con excelente respuesta, recibiendo luego como mantenimiento tofacitinib 5 mg/día. En abril de este año presenta lesiones nodulares y eritematosas en ambos miembros inferiores que luego se necrotizan y esfacelan. Se suspende tratamiento inmunosupresor. Se indica biopsia de piel que muestra linfoma T cutáneo con compromiso dérmico e hipodérmico. Se inició quimioterapia CHOP pero luego del segundo ciclo el paciente presenta aplasia medular y fallece

Estratificación de riesgo cardiovascular en enfermedades autoinmunes en un hospital universitario / Cardiovascular risk stratification in autoimmune diseases in a university hospital

Introducción: las enfermedades autoinmunes (EAI) han sido consideradas como no fatales; sin embargo, la mayoría de éstas tienen una historia natural de mortalidad prematura. Algunas como el lupus eritematoso sistémico (LES), artritis reumatoidea (AR), esclerosis sistémica (ES), polimiositis, vasculitis y otras, están asociadas a una mortalidad temprana comparable a las enfermedades cardiovasculares y neoplásicas. Objetivos: 1- identificar las EAI con mayor riesgo cardiovascular previamente diagnosticadas en pacientes que sean atendidos en un servicio de reumatología de un hospital universitario. 2- comparar el riesgo cardiovascular calculado según la escala de Framingham y el modelo SCORE en pacientes con diagnóstico previo de enfermedad autoinmune. Material y métodos: estudio analítico de corte transversal, en un servicio de reumatología de un hospital universitario donde se reclutaron 129 historias clínicas de pacientes que acudieron espontáneamente entre el 1 de noviembre de 2010 y el 31 de mayo de 2011. Se elaboraron tablas de cruces de variables y su posterior cálculo con Chi Cuadrado y coeficiente de Pearson. Resultados: las EAI con mayor riesgo cardiovascular fueron AR, vasculitis y EASN. La escala de Framingham mostró solo un paciente con AR que tenía RCV muy elevado. Las vasculitis encabezó el RCV elevado con el 16,7%, pero esto corresponde solo a un paciente. El segundo lugar estaba representado por AR (10.7%), luego EASN (10%) y LES (4,5%). El modelo SCORE demostró que el 3,1% de las enfermedades tenía muy elevado RCV, porcentaje que estaba comprendido por 3 pacientes con AR y 1 con vasculitis. El RCV elevado estuvo representado sólo por AR en un 13.3%. Al comparar ambas escalas de riesgo cardiovascular, el 70,5% de 129 pacientes presentaron bajo RCV. Sólo un paciente (0,8%) con bajo RCV en la escala de Framingham tenía muy elevado RCV en el SCORE.(AU)

Introduction :Autoimmune diseases (AID) have been considered asnon-fatal; however, most of these have a natural history of premature mortality. Some such as lupus erythematosus (SLE), rheumatoid arthri-tis (RA), systemic sclerosis (SS), polymyositis, vasculitis and others are associated with early mortality comparable to cardiovascular and neo-plastic diseases. Objectives: 1- Identify autoimmune diseases with increased cardiovascular risk in previously diagnosed patients who are treated at a rheumatology service of an university hospital. 2- To compare the cardiovascular risk calculated according to the Framingham and the SCORE modelin patients with a previous diagnosis of autoimmune disease treated ata rheumatology service of a public hospital. (AU)

Estratificación de riesgo cardiovascular en enfermedades autoinmunes en un hospital universitario / Cardiovascular risk stratification in autoimmune diseases in a university hospital

Introducción: las enfermedades autoinmunes (EAI) han sido consideradas como no fatales; sin embargo, la mayoría de éstas tienen una historia natural de mortalidad prematura. Algunas como el lupus eritematoso sistémico (LES), artritis reumatoidea (AR), esclerosis sistémica (ES), polimiositis, vasculitis y otras, están asociadas a una mortalidad temprana comparable a las enfermedades cardiovasculares y neoplásicas. Objetivos: 1- identificar las EAI con mayor riesgo cardiovascular previamente diagnosticadas en pacientes que sean atendidos en un servicio de reumatología de un hospital universitario. 2- comparar el riesgo cardiovascular calculado según la escala de Framingham y el modelo SCORE en pacientes con diagnóstico previo de enfermedad autoinmune. Material y métodos: estudio analítico de corte transversal, en un servicio de reumatología de un hospital universitario donde se reclutaron 129 historias clínicas de pacientes que acudieron espontáneamente entre el 1 de noviembre de 2010 y el 31 de mayo de 2011. Se elaboraron tablas de cruces de variables y su posterior cálculo con Chi Cuadrado y coeficiente de Pearson. Resultados: las EAI con mayor riesgo cardiovascular fueron AR, vasculitis y EASN. La escala de Framingham mostró solo un paciente con AR que tenía RCV muy elevado. Las vasculitis encabezó el RCV elevado con el 16,7%, pero esto corresponde solo a un paciente. El segundo lugar estaba representado por AR (10.7%), luego EASN (10%) y LES (4,5%). El modelo SCORE demostró que el 3,1% de las enfermedades tenía muy elevado RCV, porcentaje que estaba comprendido por 3 pacientes con AR y 1 con vasculitis. El RCV elevado estuvo representado sólo por AR en un 13.3%. Al comparar ambas escalas de riesgo cardiovascular, el 70,5% de 129 pacientes presentaron bajo RCV. Sólo un paciente (0,8%) con bajo RCV en la escala de Framingham tenía muy elevado RCV en el SCORE.

Introduction :Autoimmune diseases (AID) have been considered asnon-fatal; however, most of these have a natural history of premature mortality. Some such as lupus erythematosus (SLE), rheumatoid arthri-tis (RA), systemic sclerosis (SS), polymyositis, vasculitis and others are associated with early mortality comparable to cardiovascular and neo-plastic diseases. Objectives: 1- Identify autoimmune diseases with increased cardiovascular risk in previously diagnosed patients who are treated at a rheumatology service of an university hospital. 2- To compare the cardiovascular risk calculated according to the Framingham and the SCORE modelin patients with a previous diagnosis of autoimmune disease treated ata rheumatology service of a public hospital.

Reacción dermatológica fatal después de infiximab / Fatal skin reaction alter infliximb

El uso de agentes biológicos es cada vez más frecuente en todos los grupos etarios y aún se desconoce en su totalidad el abanico de efectos adversos a corto y largo plazo que estas drogas pueden causar. Se presenta el caso de una paciente de 73 años con una reacción severa a terapia biológica con anti-TNF (infliximab) que lleva a complicaciones graves y posteriormente a la muerte.

Reacción dermatológica fatal después de infiximab / Fatal skin reaction alter infliximb

El uso de agentes biológicos es cada vez más frecuente en todos los grupos etarios y aún se desconoce en su totalidad el abanico de efectos adversos a corto y largo plazo que estas drogas pueden causar. Se presenta el caso de una paciente de 73 años con una reacción severa a terapia biológica con anti-TNF (infliximab) que lleva a complicaciones graves y posteriormente a la muerte.(AU)

[Use of intravenous humana immunoglobulin in rheumatic diseases]. / Uso de inmunogtlobulina G humana endovenosa(IGEV) en enfermedades reumáticas.

INTRODUCTION: Preparations of intravenous immunoglobulin (IVIG) are used as treatment in different diseases such primary and secondary immunodeficiencies, autoimmune diseases, systemic inflammatory diseases, infectious diseases and allergic diseases among others. OBJECTIVE: to present 13 of our cases with the use of IVIG in different rheumatic diseases. PATIENTS AND METHODS: we retrospectively studied 13 patients (10 women and 3 men), mean age 29 years with different rheumatic diseases, that underwent conventional treatments without positive response. They received IVIG pulses, trying to improve or induce remission of their previous clinical situation. 6/13 patients met criteria for systemic lupus erythematosus (SLE), 2/13 had primary antiphospholipid syndrome (APL)one had polydermatomyositis (PDM), 1 juvenile arthritis, 1 panarteritis nodosa (cutaneous PAN), one Evans syndrome, and one with autoimmune uveitis. RESULTS: 7 of them had a positive response to therapy with IGEV evaluated by clinical and biochemical parameters. They remained with conventional treatments. One patient received a new IG EV pulse after 24 months, because of panniculitis reactivation. Clinical and biochemical response was poor in 4 of them, and 2 patients died. CONCLUSION: IVIg may be usefull in autoimmune rheumatic diseases when conventional therapies have failed. The therapeutic success is also limited. Only the 55 percent of our patients had a positive clinical response.

Impacto en la calidad de vida del paciente reumatoidea en la provincia de Cordoba

La artritis reumatoidea (A.R.) es una enfermedad generalizada del tejido conectivo (t.c.), de causa desconocida, que se caracteriza por lesiones inflamatorias que afectan a las articulaciones diartrodiales periféricas, y compromiso visceral. Aunque la A.R. discapacita a muchos cada año, mata relativamente a pocos si uno la compara con el cáncer o la enfermedad cardiovascular; sin embargo, "no existe otro grupo de enfermedades que provoque tanto sufrimiento a tantas personas durante tanto tiempo" como las enfermedades reumáticas. A causa de su tendencia a incapacitar y a dejar individuos con deterioros pero sin matarlos, la A.R. y otros reumatismos en general pertenecen a aquel grupo de enfermedades que más participación tienen desde el punto de vista de su importancia social y económica. Se estima que la prevalencia de A.R. en la raza caucásica es de aproximadamente el 0,6 por ciento mientras que la incidencia sería de 1 a 3 cada 1000 habitantes por año. Como es de esperar, esta enfermedad y su duración afectan la capacidad de trabajo de los pacientes, y muchos de ellos pueden llegar a cierto grado de incapacidad laboral desde los primeros años de la enfermedad. El presente trabajo trata de mostrar el impacto sobre la calidad de vida del paciente con artritis reumatoidea en la provincia de Córdoba. Esto implica tener una visión importante de las reales consecuencias de la enfermedad sobre el paciente artrítico; además, conocer las limitaciones funcionales, deterioros y discapacidades del mismo a través de las actividades comunes de la vida diaria y del cumplimiento de sus roles como persona independiente, o sea, de su impacto físico, mental, afectivo y social...(AU)

Impacto en la calidad de vida del paciente reumatoidea en la provincia de Cordoba

La artritis reumatoidea (A.R.) es una enfermedad generalizada del tejido conectivo (t.c.), de causa desconocida, que se caracteriza por lesiones inflamatorias que afectan a las articulaciones diartrodiales periféricas, y compromiso visceral. Aunque la A.R. discapacita a muchos cada año, mata relativamente a pocos si uno la compara con el cáncer o la enfermedad cardiovascular; sin embargo, "no existe otro grupo de enfermedades que provoque tanto sufrimiento a tantas personas durante tanto tiempo" como las enfermedades reumáticas. A causa de su tendencia a incapacitar y a dejar individuos con deterioros pero sin matarlos, la A.R. y otros reumatismos en general pertenecen a aquel grupo de enfermedades que más participación tienen desde el punto de vista de su importancia social y económica. Se estima que la prevalencia de A.R. en la raza caucásica es de aproximadamente el 0,6 por ciento mientras que la incidencia sería de 1 a 3 cada 1000 habitantes por año. Como es de esperar, esta enfermedad y su duración afectan la capacidad de trabajo de los pacientes, y muchos de ellos pueden llegar a cierto grado de incapacidad laboral desde los primeros años de la enfermedad. El presente trabajo trata de mostrar el impacto sobre la calidad de vida del paciente con artritis reumatoidea en la provincia de Córdoba. Esto implica tener una visión importante de las reales consecuencias de la enfermedad sobre el paciente artrítico; además, conocer las limitaciones funcionales, deterioros y discapacidades del mismo a través de las actividades comunes de la vida diaria y del cumplimiento de sus roles como persona independiente, o sea, de su impacto físico, mental, afectivo y social...

Impacto en la calidad de vida del paciente reumatoidea en la provincia de Cordoba

La artritis reumatoidea (A.R.) es una enfermedad generalizada del tejido conectivo (t.c.), de causa desconocida, que se caracteriza por lesiones inflamatorias que afectan a las articulaciones diartrodiales periféricas, y compromiso visceral. Aunque la A.R. discapacita a muchos cada año, mata relativamente a pocos si uno la compara con el cáncer o la enfermedad cardiovascular; sin embargo, "no existe otro grupo de enfermedades que provoque tanto sufrimiento a tantas personas durante tanto tiempo" como las enfermedades reumáticas. A causa de su tendencia a incapacitar y a dejar individuos con deterioros pero sin matarlos, la A.R. y otros reumatismos en general pertenecen a aquel grupo de enfermedades que más participación tienen desde el punto de vista de su importancia social y económica. Se estima que la prevalencia de A.R. en la raza caucásica es de aproximadamente el 0,6 por ciento mientras que la incidencia sería de 1 a 3 cada 1000 habitantes por año. Como es de esperar, esta enfermedad y su duración afectan la capacidad de trabajo de los pacientes, y muchos de ellos pueden llegar a cierto grado de incapacidad laboral desde los primeros años de la enfermedad. El presente trabajo trata de mostrar el impacto sobre la calidad de vida del paciente con artritis reumatoidea en la provincia de Córdoba. Esto implica tener una visión importante de las reales consecuencias de la enfermedad sobre el paciente artrítico; además, conocer las limitaciones funcionales, deterioros y discapacidades del mismo a través de las actividades comunes de la vida diaria y del cumplimiento de sus roles como persona independiente, o sea, de su impacto físico, mental, afectivo y social...(AU)