RESUMO
BACKGROUND/OBJECTIVE: The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria (2019 AECC) for IgG4-related disease (IgG4-RD) is considered a significant advancement in the study of this condition. Most studies evaluating their performance have focused on White and Asian patients, leaving a knowledge gap regarding Latin American populations. Therefore, this study aimed to assess the performance of the 2019 AECC for IgG4-RD in a cohort of Latin American patients. METHODS: A multicenter medical records review study was conducted, involving centers from Argentina, Chile, Mexico, Peru, and Uruguay. Data on IgG4-RD patients and mimicker conditions were collected through a standardized online form. The criterion standard for diagnosing IgG4-RD was based on the fulfillment of the Comprehensive Diagnostic Criteria for IgG4-RD and/or the Consensus Statement on Pathology. The 2019 AECC was retrospectively applied. RESULTS: We included 300 patients, with 180 (60%) having IgG4-RD and 120 (40%) having mimicker conditions. The 2019 AECC had a sensitivity of 66.7% and a specificity of 100%. Sensitivity increased to 73.3% when disease-specific autoantibody items were removed, without affecting specificity. The true-positive cases had more involved organs, a higher availability of biopsy results, and were more likely to belong to the Mikulicz/systemic and proliferative phenotypes. CONCLUSIONS: The use of the 2019 AECC for IgG4-RD in a Latin American population confirms its high specificity in excluding those without the disease. The presence of concomitant autoimmune diseases and clinically nonsignificant disease-specific autoantibodies excludes a significant number of patients from fulfilling the criteria.
Assuntos
Doença Relacionada a Imunoglobulina G4 , Doenças Reumáticas , Reumatologia , Humanos , Estados Unidos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Estudos Retrospectivos , América Latina , Doenças Reumáticas/diagnóstico , AutoanticorposAssuntos
Doenças Autoimunes , COVID-19 , Vacinas , Vacinas contra COVID-19 , Tomada de Decisões , Humanos , SARS-CoV-2 , IncertezaRESUMO
Autoimmune diseases are chronic inflammatory pathologies that are characterized by the presence of antibodies against the body's own epitopes in serum (autoantibodies). Systemic lupus erythematosus (SLE) is a common autoimmune pathology characterized by the presence of antinuclear antibodies (ANAs). These include anti-dsDNA (α-dsDNA) antibodies, which are widely used for diagnosis and disease monitoring. Their determination is carried out using traditional techniques such as Indirect Immunofluorescence (IFI) or Enzyme-Linked Immunosorbent Assay (ELISA), which are time consuming, require qualified technicians, and are not compatible with decentralized analysis outside a laboratory facility. Here, we show a sandwich-format electrochemical biosensor-based method for α-dsDNA determination in a rapid and simple manner. The total assay time is only 30 minutes, and the sensor is capable of detecting 16 ng (8 µg mL-1) of α-dsDNA antibodies. Using the current derived from the detection limit of the method as a cut-off, we could discriminate positive from negative serum samples with 90% sensitivity and 100% specificity. Using monoclonal antibodies for calibration curves, our results are presented in absolute scale (i.e., concentration instead of serum titer) which will help us to perform comparisons between methods and carry out further improvements of this protocol. In an effort to render the sensor compatible with automation, we minimized the manipulation steps without compromising the analytical performance, even in complex samples such as serum.
Assuntos
Anticorpos Antinucleares/sangue , Técnicas Biossensoriais , Lúpus Eritematoso Sistêmico/diagnóstico , Técnicas Eletroquímicas , Humanos , Sensibilidade e EspecificidadeRESUMO
Antimalarials have demonstrated beneficial effects in Systemic Lupus Erithematosus and Rheumatoid Arthritis. However, the mechanisms and the molecular players targeted by these drugs remain obscure. Although hydroxychloroquine (HCQ) is a known ion channel inhibitor, this property has not been linked to its anti-inflammatory effects. We aimed to study whether HCQ inhibits pro-inflammatory ion channels. Electrophysiology experiments demonstrated that HCQ inhibited Ca++-activated K+ conductance in THP-1 macrophages in a dose-dependent manner. In macrophages, ATP-induced K+ efflux plays a key role in activating the NLRP3 inflammasome. ATP-induced IL-1beta secretion was controlled by the KCa1.1 inhibitor iberiotoxin. NS1619 and NS309 (KCa1.1 and KCa3.1 activators respectively) induced the secretion of IL-1beta. This effect was inhibited by HCQ and also by iberiotoxin and clotrimazol (KCa3.1 inhibitor), arguing against off-target effect. In vitro, HCQ inhibited IL-1beta and caspase 1 activation induced by ATP in a dose-dependent manner. HCQ impaired K+ efflux induced by ATP. In vivo, HCQ inhibited caspase 1-dependent ATP-induced neutrophil recruitment. Our results show that HCQ inhibits Ca++-activated K+ channels. This effect may lead to impaired inflammasome activation. These results are the basis for i) a novel anti-inflammatory mechanism for HCQ and ii) a new strategy to target pro-rheumatic Ca++-activated K+ channels.
Assuntos
Hidroxicloroquina/farmacologia , Inflamassomos/metabolismo , Ativação do Canal Iônico/efeitos dos fármacos , Canais de Potássio Cálcio-Ativados/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Biomarcadores , Caspase 1/genética , Caspase 1/metabolismo , Humanos , CamundongosRESUMO
BACKGROUND: End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). OBJECTIVES: To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. RESULTS: Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36±10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n=12), acute rejection (n=2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P=0.007) and positive anti-HCV antibodies (P=0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. CONCLUSION: Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure.
Assuntos
Falência Renal Crônica/cirurgia , Lúpus Eritematoso Sistêmico/cirurgia , Prognóstico , Adulto , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Transplante de Rim/mortalidade , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Se analiza el caso clínico de una paciente de 48 años que consulta por debilidad muscular. Se enfatiza la importancia del examen neurológico para definir el planteo diagnóstico. Se esquematiza el razonamiento clínico en un paciente con síndrome miopático y los estudios paraclínicos a solicitar. A propósito de este caso clínico se discute el sreening diagnóstico para cáncer oculto en pacientes con miopatía inflamatoria tipo polimiositis y las posibilidades terapéuticas.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Miosite/diagnóstico , Miosite/etiologia , Miosite/terapia , Polimiosite/diagnóstico , Polimiosite/etiologia , Polimiosite/terapia , Neoplasias , Exames MédicosRESUMO
RESUMEN: Arch Med Interna 2013 - 35(1):15-18 Se analiza el caso clínico de una paciente de 48 años que consulta por debilidad muscular. Se enfatiza la importancia del examen neurológico para definir el planteo diagnóstico. Se esquematiza el razonamiento clínico en un paciente con síndrome miopático y los estudios paraclínicos a solicitar. A propósito de este caso clínico se discute el sreening diagnóstico para cáncer oculto en pacientes con miopatía inflamatoria tipo polimiositis y las posibilidades terapéuticas.
ABSTRACT: Arch Med Interna 2013 - 35(1):15-18 This report analyses a clinical case of a 48 years old woman with muscular weakness. The relevance of neurology exam to define the diagnosis is emphasized. Clinical reasoning in a patient with myopatic syndrome and its studies are schematized. Screening for occult malignancy in a patient with polymiositis and its therapy is discussed.
RESUMO
Introducción: la capilaroscopía del pliegue ungueal (CPU) consiste en la observación in vivo de la microcirculación capilar, donde habitualmente pueden describirse tres patrones (tortuoso, esclerodermiforme y normal). Objetivo: describir las alteraciones capilares en pacientes queconsultaron en la Unidad de Enfermedades Autoinmunes Sistémicasdel Hospital de Clínicas entre agosto de 2009 y octubre de 2010. Pacientes, materiales y métodos: realizamos un estudio descriptivo, retrospectivo, cualitativo de los patrones capilaroscópicos. Resultados: se revisaron historias clínicas y CPU de 110 pacientes (102 mujeres), con una media de edad 46,6 ± 17,5 años siendo el grupo mayoritario representado por 34 (31%) pacientes con esclerosis sistémica. Los patrones en la CPUhallados fueron normales en 38% y patológicos en 62% de los pacientes. El 88% de los pacientes con esclerosis sistémica presentaron una CPU patológica, de estos, 74% correspondióa un patrón esclerodermiforme. En pacientes con enfermedades autoinmunes (exceptuando la esclerosis sistémica) encontramos un patrón patológico en 66% (27% correspondieron a un patrón esclerodermiforme). Conclusiones: la CPU contribuyó en distintos aspectos en el estudio del fenómeno de Raynaud y de enfermedades autoinmunes. La detección de un patrón esclerodermiforme fue altamentesugestiva de la presencia de una enfermedad autoinmune sistémica. La CPU, junto a los hallazgos clínicos y marcadores biológicos adecuados, adquiere valor y especificidad en el diagnóstico, debiendo formar parte de la valoración clínica de pacientes con fenómeno de Raynaud y sospecha clínicao analítica de enfermedades autoinmunes sistémicas. (AU)
Introduction: nailfold capillaroscopy (NC) consists of the in vivo observation of capillary microcirculation, which usually presents three patterns (tortuos, sclerodermiform and normal).Objective: to describe capillary alterations in patients who consulted at the Systemic Autoimmune DiseasesUnit of the Clínicas Hospital, between August 2009 and October 2010.Patients, material and methods: we conducted a descriptive, retrospective and qualitative study of capillaroscopypatterns. Results: the medical records and NC of 110 patients were reviewed (102 women), average age was 46.6 ±17.5 years old, being the largest group represented by 34 (31%) patients with systemic sclerosis. Patterns foundin the NC were normal in 38% of cases and pathological in 62% of them. Eighty eight per cent of patients withsystemic sclerosis presented a pathological NC, and 74% of the latter corresponded to a sclerodermiformpattern. We found a pathololgical pattern in 66% of patients with autoimmune diseases (except for systemic sclerosis), where 27% corresponded to a sclerodermiformpattern. Conclusions: NC contributed to the study of the Raynaud phenomenon and autoinmune diseases indifferent ways. Identifying a sclerodermiform pattern highly suggested the presence of a systemic autoimmune disease. The NC, together with clinical findings and the appropriate biological markers gains value and specificity in the diagnosis, and it thus should be a part of the clinical assessment of patients with the Raynauds disease and a clinical or analytical suspicion of systemicautoimmune disease. (AU)
Introduçäo: a capilaroscopia periungueal (CPU) consiste na observaçao in vivo da rede microvascular da regiäo periungueal, onde habitualmente se podem descrevertrês padrões: tortuoso, esclerodermiforme e normal.Objetivo: descrever as alterações capilares em pacientes que consultaram na Unidade de Doenças Auto-imunes Sistêmicas do Hospital de Clínicas entreagosto de 2009 e outubro de 2010.Pacientes, materiais e métodos: realizamos um estudio descritivo, retrospectivo, qualitativo dos padrões capilaroscópicos. Resultados: revisamos o prontuário médico e CPU de 110 pacientes (102 mulheres), com idade média de 46.6 ± 17.5 anos; 34 (31%) eram pacientes com esclerose sistêmica. Os padrões encontrados na CPU foramnormais em 38% e patológicos em 62% dos pacientes. 88% dos pacientes com esclerose sistêmica apresentaramCPU patológica; destes, 74% correspondeu a um padräo esclerodermiforme. En pacientes com doenças auto-imunes (excluindo a esclerose sistêmica) encontramos um padräo patológico em 66% (27% correspondeu a um padräo esclerodermiforme). Conclusões: a CPU contribuiu em diferentes aspectosao estudo do fenômeno de Raynaud e de doenças auto-imunes.Adetecçäo de umpadräo esclerodermiforme foi um forte indicio da presença de uma enfermedad auto-imune sistêmica. A CPU, juntamente com outros aspectosclínicos e marcadores biológicos adequados, tem valor e especificidade no diagnóstico, devendo formar parte da avaliaçäo clínica de pacientes com fenômeno de Raynaud e suspeita clínica ou analítica de doenças auto-imunes sistêmicas. (AU)
Assuntos
Angioscopia Microscópica , Doenças Autoimunes/diagnósticoRESUMO
Introducción: la capilaroscopía del pliegue ungueal (CPU) consiste en la observación in vivo de la microcirculación capilar, donde habitualmente pueden describirse tres patrones (tortuoso, esclerodermiforme y normal). Objetivo: describir las alteraciones capilares en pacientes queconsultaron en la Unidad de Enfermedades Autoinmunes Sistémicasdel Hospital de Clínicas entre agosto de 2009 y octubre de 2010. Pacientes, materiales y métodos: realizamos un estudio descriptivo, retrospectivo, cualitativo de los patrones capilaroscópicos. Resultados: se revisaron historias clínicas y CPU de 110 pacientes (102 mujeres), con una media de edad 46,6 ± 17,5 años siendo el grupo mayoritario representado por 34 (31%) pacientes con esclerosis sistémica. Los patrones en la CPUhallados fueron normales en 38% y patológicos en 62% de los pacientes. El 88% de los pacientes con esclerosis sistémica presentaron una CPU patológica, de estos, 74% correspondióa un patrón esclerodermiforme. En pacientes con enfermedades autoinmunes (exceptuando la esclerosis sistémica) encontramos un patrón patológico en 66% (27% correspondieron a un patrón esclerodermiforme). Conclusiones: la CPU contribuyó en distintos aspectos en el estudio del fenómeno de Raynaud y de enfermedades autoinmunes. La detección de un patrón esclerodermiforme fue altamentesugestiva de la presencia de una enfermedad autoinmune sistémica. La CPU, junto a los hallazgos clínicos y marcadores biológicos adecuados, adquiere valor y especificidad en el diagnóstico, debiendo formar parte de la valoración clínica de pacientes con fenómeno de Raynaud y sospecha clínicao analítica de enfermedades autoinmunes sistémicas.
Introduction: nailfold capillaroscopy (NC) consists of the in vivo observation of capillary microcirculation, which usually presents three patterns (tortuos, sclerodermiform and normal).Objective: to describe capillary alterations in patients who consulted at the Systemic Autoimmune DiseasesUnit of the Clínicas Hospital, between August 2009 and October 2010.Patients, material and methods: we conducted a descriptive, retrospective and qualitative study of capillaroscopypatterns. Results: the medical records and NC of 110 patients were reviewed (102 women), average age was 46.6 ±17.5 years old, being the largest group represented by 34 (31%) patients with systemic sclerosis. Patterns foundin the NC were normal in 38% of cases and pathological in 62% of them. Eighty eight per cent of patients withsystemic sclerosis presented a pathological NC, and 74% of the latter corresponded to a sclerodermiformpattern. We found a pathololgical pattern in 66% of patients with autoimmune diseases (except for systemic sclerosis), where 27% corresponded to a sclerodermiformpattern. Conclusions: NC contributed to the study of the Raynaud phenomenon and autoinmune diseases indifferent ways. Identifying a sclerodermiform pattern highly suggested the presence of a systemic autoimmune disease. The NC, together with clinical findings and the appropriate biological markers gains value and specificity in the diagnosis, and it thus should be a part of the clinical assessment of patients with the RaynaudÆs disease and a clinical or analytical suspicion of systemicautoimmune disease.
Introdução: a capilaroscopia periungueal (CPU) consiste na observaçao in vivo da rede microvascular da região periungueal, onde habitualmente se podem descrevertrês padrões: tortuoso, esclerodermiforme e normal.Objetivo: descrever as alterações capilares em pacientes que consultaram na Unidade de Doenças Auto-imunes Sistêmicas do Hospital de Clínicas entreagosto de 2009 e outubro de 2010.Pacientes, materiais e métodos: realizamos um estudio descritivo, retrospectivo, qualitativo dos padrões capilaroscópicos. Resultados: revisamos o prontuário médico e CPU de 110 pacientes (102 mulheres), com idade média de 46.6 ± 17.5 anos; 34 (31%) eram pacientes com esclerose sistêmica. Os padrões encontrados na CPU foramnormais em 38% e patológicos em 62% dos pacientes. 88% dos pacientes com esclerose sistêmica apresentaramCPU patológica; destes, 74% correspondeu a um padrão esclerodermiforme. En pacientes com doenças auto-imunes (excluindo a esclerose sistêmica) encontramos um padrão patológico em 66% (27% correspondeu a um padrão esclerodermiforme). Conclusões: a CPU contribuiu em diferentes aspectosao estudo do fenômeno de Raynaud e de doenças auto-imunes.Adetecção de umpadrão esclerodermiforme foi um forte indicio da presença de uma enfermedad auto-imune sistêmica. A CPU, juntamente com outros aspectosclínicos e marcadores biológicos adequados, tem valor e especificidade no diagnóstico, devendo formar parte da avaliação clínica de pacientes com fenômeno de Raynaud e suspeita clínica ou analítica de doenças auto-imunes sistêmicas.
Assuntos
Angioscopia Microscópica , Doenças Autoimunes/diagnósticoRESUMO
La enfermedad tromboembólica venosa (ETEV) es la principal causa de morbimortalidad materna, seguida en segundo lugar por las hemorragias. La primera da cuenta de 19,6% de las muertes obstétricas. Presentamos el caso clínico de una paciente de 29 años con mala historia obstétrica, que cursando la cuarta gesta instala una embolia pulmonar bilateral seguida por la pérdida del embarazo. No se logró atribuir a ninguna de las trombofilias conocidas hasta el momento la responsabilidad de la misma, a pesar de la alta incidencia (50%) de trombofilias en la población embarazada con ETEV.
Venous thromboembolism (VTE) is the main cause of maternal morbimortality, followed by hemorrhage. Thethromboembolic disease accounts for 19.6 % of obstetric deaths. The study presents the clinical case of a 29 year old patient with a bad obstetric history, who, pregnant with her fourth child evidenced bilateral pulmonary embolism and subsequently lost her pregnancy. The cause of death could not be attributed to any of the thromboembolisms known until today, in spite of the high incidence (50%) of thromboembolic diseases in thepregnant population with venous thromboembolism.
Adoença tromboembólica venosa (TEV)é a principal causa de morbimortalidade materna, seguida pelas hemorragias.A TEV é responsável por 19,6% dasmortes obstétricas. Apresentamos o caso clínico de uma paciente de 29anos com história obstétrica problemática, que em sua quarta gestação instala una embolia pulmonar bilateral seguida por perda da gravidez. Não foi possível relacionar sua etiologia com nenhuma das trombofilias conhecidas até omomento apesar da alta incidência (50%) de trombofilias na população de gestantes com TEV.