ABSTRACT
OBJECTIVE: To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK). METHODS: A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members. RESULTS: Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible. CONCLUSION: The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries.
Subject(s)
Rheumatology , Takayasu Arteritis , Humans , United States , Takayasu Arteritis/diagnosis , Takayasu Arteritis/drug therapy , Tumor Necrosis Factor Inhibitors/therapeutic use , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic useABSTRACT
Considerable variability exists in the way health-care providers treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in Latin America. The most frequently used treatments for ANCA-associated vasculitis are cyclophosphamide and prolonged glucocorticoid tapers; however, randomised controlled trials conducted over the past 30 years have led to the development of several evidence-based treatment alternatives for these patients. Latin America faces socioeconomic challenges that affect access to care, and the use of certain costly medications with proven efficacy ANCA-associated vasculitis is often restricted. For these reasons, the Pan American League of Associations for Rheumatology developed the first ANCA-associated vasculitis treatment guidelines tailored for Latin America. A panel of local vasculitis experts generated clinically meaningful questions related to the treatment of ANCA-associated vasculitis using the Population, Intervention, Comparator, and Outcome (PICO) format. Following the Grading of Recommendations Assessment, Development, and Evaluation methodology, a team of methodologists conducted a systematic literature review. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members. 21 recommendations and two expert opinion statements for the treatment of ANCA-associated vasculitis were developed, considering the current evidence and the socioeconomic characteristics of the region. These recommendations include guidance for the use of glucocorticoids, non-glucocorticoid immunosuppressants, and plasma exchange.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Rheumatology , Humans , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Antibodies, Antineutrophil Cytoplasmic , Glucocorticoids/therapeutic use , Plasma Exchange , PlasmapheresisABSTRACT
La arteritis de células gigantes (ACG) es una vasculitis sistémica que afecta a personas adultas; compromete vasos arteriales de mediano y gran calibre, con potenciales complicaciones de gravedad, como la ceguera, y es considerada una emergencia médica. El objetivo de estas guías fue desarrollar las primeras recomendaciones argentinas para su tratamiento, basadas en la revisión de la literatura mediante metodología GRADE. Un panel de expertos en vasculitis elaboró las preguntas en formato PICO (población, intervención, comparador y outcomes), y luego un panel de expertos en metodología efectuó la revisión de la bibliografía con la extracción de la evidencia para cada una de las preguntas. Se realizó un focus group de pacientes para conocer sus preferencias y experiencias. Finalmente, con la información recabada, el panel de expertos en vasculitis procedió a la votación de las recomendaciones que a continuación se presentan.
Giant cell arteritis (GCA) is a systemic vasculitis affecting adult patients and involving large and medium vessels. Potential serious complications as blindness may occur and it is considered a medical emergency. The objective of elaborating this guideline was to develop first Argentinian GCA treatment recommendations using GRADE methodology. An expert panel generated clinically meaningful questions addressing aspects of the treatment of GCA in the Population, Intervention, Comparator and Outcome (PICO) format and then a group of methodology experts reviewed and extracted data from literature summarizing available evidence. A patient's focus group discussion took place gathering information on their preferences and experiences. Finally, the vasculitis expert panel, with all the information obtained, voted recommendations here presented.
Subject(s)
Giant Cell Arteritis , Rheumatology , Therapeutics , VasculitisABSTRACT
La arteritis de células gigantes (ACG) es una vasculitis sistémica que afecta a personas adultas; compromete vasos arteriales de mediano y gran calibre, con potenciales complicaciones de gravedad, como la ceguera, y es considerada una emergencia médica. El objetivo de estas guías fue desarrollar las primeras recomendaciones argentinas para su tratamiento, basadas en la revisión de la literatura mediante metodología GRADE. Un panel de expertos en vasculitis elaboró las preguntas en formato PICO (población, intervención, comparador y outcomes), y luego un panel de expertos en metodología efectuó la revisión de la bibliografía con la extracción de la evidencia para cada una de las preguntas. Se realizó un focus group de pacientes para conocer sus preferencias y experiencias. Finalmente, con la información recabada, el panel de expertos en vasculitis procedió a la votación de las recomendaciones que a continuación se presentan.
Subject(s)
Giant Cell Arteritis , Therapeutics , VasculitisABSTRACT
Considerable variability exists in the way that health-care providers treat patients with giant cell arteritis in Latin America, with patients commonly exposed to excessive amounts of glucocorticoids. In addition, large health disparities prevail in this region due to socioeconomic factors, which influence access to care, including biological treatments. For these reasons, the Pan American League of Associations for Rheumatology developed the first evidence-based giant cell arteritis treatment guidelines tailored for Latin America. A panel of vasculitis experts from Mexico, Colombia, Peru, Brazil, and Argentina generated clinically meaningful questions related to the treatment of giant cell arteritis in the population, intervention, comparator, and outcome (PICO) format. Following the grading of recommendations, assessment, development, and evaluation methodology, a team of methodologists did a systematic literature search, extracted and summarised the effects of the interventions, and graded the quality of the evidence. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members to be included in the guidelines. Nine recommendations and one expert opinion statement for the treatment of giant cell arteritis were developed considering the most up-to-date evidence and the socioeconomic characteristics of Latin America. These recommendations include guidance for the use of glucocorticoids, tocilizumab, methotrexate, and aspirin for patients with giant cell arteritis.
Subject(s)
Giant Cell Arteritis , Rheumatology , Humans , Giant Cell Arteritis/drug therapy , Argentina , Aspirin , Brazil , Glucocorticoids/therapeutic useABSTRACT
Abstract The epidemiology of pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), has not been evaluated in our country, therefore there is no reference parameter to establishing the representativeness of this information in the national order. This registry represents the first collaborative effort to provide a knowledge base of this disease, including 5 scientific societies that represent different specialties (pediatrics, rheumatology, pulmonology and cardiology) with data from 23 Argentine provinces. These efforts involved five societies of various adult (cardiology, rheumatology, and pulmonology) and pediatric (cardiology) specialties. Subjects were grouped (1-5) in accord with the 2013 Nice classification. A total of 627 patients (mean age, 50.8±18 years; women, 69.2%) were recruited. Incident cases accounted for 53%. Functional class III-IV accounted for 69% at time of diagnosis and 33.4% at time of inclusion. Distributions in groups 1-5 were 63.6%, 15.9%, 8.3%, 9.7%, and 2.4%, respectively. Treatment consisted of diuretics (51.2%), mineralocorticoid receptor antagonists (44.7%), digoxin (16.6%), anticoagulants (39.2%), renin-angiotensin antagonists (15.5%), beta blockers (15.6%), and calcium channel blockers (8%). Rates of specific therapies usage in PAH vs. non-PAH group were 80.5% vs. 40.8% (phosphodiesterase-5 inhibitors: 71% vs. 38.6%; endothelin receptor antagonists: 54.4% vs. 14.5%; prostanoids: 14.3 vs. 3.1%; all p < 0.001). Three-year survival in PAH and non-PAH differed significantly (82.8% vs. 73.3%; p = 0.001). In the Argentine RECOPILAR registry, the clinic-epidemiologic profile was that of advanced-stage disease. Diagnostic workups and therapeutics interventions, including use of specific therapy for PAH, were consistent with current recommendations. Despite delays in diagnosis, survival was aligned with other contemporary registries.
Resumen La epidemiología de la hipertensión pulmonar (HP), especialmente la arterial (HAP), no ha sido evaluada en nuestro país, por lo cual no existe un parámetro de referencia para establecer la representatividad de esta información en el orden nacional. El presente registro representa el primer esfuerzo colaborativo para una base de conocimiento de esta enfermedad, incluyendo 5 sociedades científicas que representan a distintas especiali dades médicas (pediatría, reumatología, neumonología y cardiología) con datos de 23 provincias argentinas. Los sujetos se agruparon (1-5) de acuerdo con la clasificación de Niza de 2013. El seguimiento se completó en 583 pacientes (93%) un año después del final de la inscripción. Se incluyeron 627 pacientes (edad media, 50.8 ± 18 años; mujeres, 69.2%). Los casos incidentes representaron el 53%. La clase funcional III-IV representaba 69% en el momento del diagnóstico y 33.4% en el momento de la inclusión. Las manifestaciones clínicas fueron disnea (81.8%), fatiga (54.1%), síncope (10.8%), dolor torácico (14.7%), palpitaciones (20.9%) e insuficiencia cardíaca (20.4%). Las tasas de uso de terapias específicas en la hipertensión arterial pulmonar (HAP) frente al grupo sin HAP fueron del 80.5% frente al 40.8%. La supervivencia a tres años en los subconjuntos de HAP y no HAP difirió significativamente (82.8% vs. 73.3%; p = 0.001). En el registro RECOPILAR argentino, que aborda principalmente la HAP, el perfil clínico-epidemiológico fue el d e una enfermedad en estadios avanzados. El diag nóstico y las intervenciones terapéuticas, incluido el uso de terapia específica para la HAP, fueron consistentes con las recomendaciones actuales.
Subject(s)
Humans , Female , Child , Adult , Middle Aged , Aged , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/therapy , Hypertension, Pulmonary/epidemiology , Argentina/epidemiology , Registries , Endothelin Receptor Antagonists , AnticoagulantsABSTRACT
The epidemiology of pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), has not been evaluated in our country, therefore there is no reference parameter to establishing the representativeness of this information in the national order. This registry represents the first collaborative effort to provide a knowledge base of this disease, including 5 scientific societies that represent different specialties (pediatrics, rheumatology, pulmonology and cardiology) with data from 23 Argentine provinces. These efforts involved five societies of various adult (cardiology, rheumatology, and pulmonology) and pediatric (cardiology) specialties. Subjects were grouped (1-5) in accord with the 2013 Nice classification. A total of 627 patients (mean age, 50.8 ± 18 years; women, 69.2%) were recruited. Incident cases accounted for 53%. Functional class III-IV accounted for 69% at time of diagnosis and 33.4% at time of inclusion. Distributions in groups 1-5 were 63.6%, 15.9%, 8.3%, 9.7%, and 2.4%, respectively. Treatment consisted of diuretics (51.2%), mineralocorticoid receptor antagonists (44.7%), digoxin (16.6%), anticoagulants (39.2%), renin-angiotensin antagonists (15.5%), beta blockers (15.6%), and calcium channel blockers (8%). Rates of specific therapies usage in PAH vs. non-PAH group were 80.5% vs. 40.8% (phosphodiesterase-5 inhibitors: 71% vs. 38.6%; endothelin receptor antagonists: 54.4% vs. 14.5%; prostanoids: 14.3 vs. 3.1%; all p < 0.001). Three-year survival in PAH and non-PAH differed significantly (82.8% vs. 73.3%; p = 0.001). In the Argentine RECOPILAR registry, the clinic-epidemiologic profile was that of advanced-stage disease. Diagnostic workups and therapeutics interventions, including use of specific therapy for PAH, were consistent with current recommendations. Despite delays in diagnosis, survival was aligned with other contemporary registries.
La epidemiología de la hipertensión pulmonar (HP), especialmente la arterial (HAP), no ha sido evaluada en nuestro país, por lo cual no existe un parámetro de referencia para establecer la representatividad de esta información en el orden nacional. El presente registro representa el primer esfuerzo colaborativo para una base de conocimiento de esta enfermedad, incluyendo 5 sociedades científicas que representan a distintas especialidades médicas (pediatría, reumatología, neumonología y cardiología) con datos de 23 provincias argentinas. Los sujetos se agruparon (1-5) de acuerdo con la clasificación de Niza de 2013. El seguimiento se completó en 583 pacientes (93%) un año después del final de la inscripción. Se incluyeron 627 pacientes (edad media, 50.8 ± 18 años; mujeres, 69.2%). Los casos incidentes representaron el 53%. La clase funcional III-IV representaba 69% en el momento del diagnóstico y 33.4% en el momento de la inclusión. Las manifestaciones clínicas fueron disnea (81.8%), fatiga (54.1%), síncope (10.8%), dolor torácico (14.7%), palpitaciones (20.9%) e insuficiencia cardíaca (20.4%). Las tasas de uso de terapias específicas en la hipertensión arterial pulmonar (HAP) frente al grupo sin HAP fueron del 80.5% frente al 40.8%. La supervivencia a tres años en los subconjuntos de HAP y no HAP difirió significativamente (82.8% vs. 73.3%; p = 0.001). En el registro RECOPILAR argentino, que aborda principalmente la HAP, el perfil clínico-epidemiológico fue el d e una enfermedad en estadios avanzados. El diagnóstico y las intervenciones terapéuticas, incluido el uso de terapia específica para la HAP, fueron consistentes con las recomendaciones actuales.
Subject(s)
Hypertension, Pulmonary , Adult , Aged , Anticoagulants , Argentina/epidemiology , Child , Endothelin Receptor Antagonists , Female , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/therapy , Middle Aged , RegistriesABSTRACT
Introduction: rheumatoid arthritis is a frequent inflammatory disease and a leading cause of potentially-treatable disability. Rheumatoid arthritis is associated with an increased risk of general morbidity and mortality. New therapeutic options have dramatically improved the evolution of patients. Objectives: in this joint work of the Association of Auditing and Quality of Medical Care of Córdoba (ASACAM) and the Argentine Society of Rheumatology (SAR), we generated recommendations to especially assist medical auditors in making decisions to improve the quality of the medical and life care of patients and reduce costs in the management of rheumatoid arthritis patients. in addition to medical auditors, these recommendations can be expanded to general practitioners, rheumatologists and clinicians, and eventually to the general public. Conclusions: suggestions for the diagnosis and treatment of patients with rheumatoid arthritis (including biological therapies) are described, based on the Clinical Practice Guidelines for the Treatment of Rheumatoid Arthritis (SAR, 2013), the resolutions of the Compulsory Medical Program and the Unique Reimbursement System currently used in Intended population: in addition to medical auditors, these recommendations can be expanded to general practitioners, rheumatologists and clinicians, and eventually to the general public. Conclusions: suggestions for the diagnosis and treatment of patients with rheumatoid arthritis (including biological therapies) are described, based on the Clinical Practice Guidelines for the Treatment of Rheumatoid Arthritis (SAR, 2013), the resolutions of the Compulsory Medical Program and the Unique Reimbursement System currently used in Argentina.
Introducción: la artritis reumatoidea es una patología inflamatoria frecuente, así como una causa destacada de incapacidad potencialmente tratable que se vincula con mayor riesgo de morbimortalidad general. Las nuevas opciones terapéuticas han mejorado de manera destacada la evolución de los pacientes. Objetivos: en este trabajo conjunto de la Asociación de Auditoria y Calidad de Atención Médica de Córdoba (ASACAM) y la Sociedad Argentina de Reumatología (SAR) se generaron recomendaciones para asistir especialmente a los médicos auditores en la toma de decisiones para mejorar la calidad de la atención médica y de vida de los pacientes y reducir los costos de las prestaciones en el enfoque de la artritis reumatoidea. Destinatarios: además de médicos auditores, estas recomendaciones pueden expandirse a médicos generales, reumatólogos y clínicos, y eventualmente al público en general. Conclusiones: se describen sugerencias para el diagnóstico y tratamiento de los pacientes con artritis reumatoidea, incluidas las terapias biológicas, sobe la base de las Guías de Práctica Clínica en el Tratamiento de la Artritis Reumatoidea (SAR, 2013), las resoluciones del Programa Médico Obligatorio y el denominado Sistema Único de Reintegro vigente en la Argentina.
Subject(s)
Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Argentina , Humans , Medical Audit , Practice Guidelines as TopicABSTRACT
Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.
Subject(s)
Antiphospholipid Syndrome/drug therapy , Hematologic Diseases/drug therapy , Kidney Diseases/drug therapy , Lupus Erythematosus, Systemic/drug therapy , Antiphospholipid Syndrome/etiology , Heart Diseases/drug therapy , Heart Diseases/etiology , Hematologic Diseases/etiology , Humans , Kidney Diseases/etiology , Latin America , Lung Diseases/drug therapy , Lung Diseases/etiology , Lupus Erythematosus, Systemic/complications , Lupus Nephritis/drug therapy , Lupus Nephritis/etiology , Mental Disorders/drug therapy , Mental Disorders/etiology , Musculoskeletal Diseases/drug therapy , Musculoskeletal Diseases/etiology , Skin Diseases/drug therapy , Skin Diseases/etiology , Standard of CareABSTRACT
Introducción: Hasta ahora el diagnóstico de la Arteritis de Células gigantes (ACg) se ha basado fundamentalmente en la clínica y la biopsia de arteria temporal y el tratamiento en corticoides. En los últimos años, han aparecido nuevos métodos que ayudan en el diagnóstico, y recientemente nuevos tratamientos. Objetivos: Describir el manejo actual de ACg en Argentina. Métodos: Una encuesta corta online de 10 preguntas, diseñada por miembros del grupo de Estudio de Vasculitis de la Sociedad Argentina de Reumatología, fue enviada vía mail a los médicos socios de la Sociedad Argentina de Reumatología (SAR). Resultados: Se obtuvieron las respuestas de 188 médicos. Solo un 13,4% de los reumatólogos estima que logra hacerle una biopsia temporal a la mayoría de sus pacientes con sospecha de ACg, mientras que un 45% puede realizarles ecodoppler. Las dosis de corticoides utilizadas y la duración del tratamiento es variable. No es frecuente el uso de otros tratamientos distintos de los corticoides. Conclusión: El uso prolongado de corticoides es el tratamiento más usado para pacientes con ACg en Argentina con escaso uso de otros inmunosupresores. El uso de ecodoppler de arteria temporal parecería estar más fácilmente disponible como herramienta diagnóstica que la biopsia
Subject(s)
Arteritis , Vasculitis , Giant CellsABSTRACT
OBJECTIVE: To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America. METHODS: Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history. RESULTS: Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (pBonferroni < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (pBonferroni = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment. CONCLUSION: Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/genetics , Genotype , Rheumatoid Factor/genetics , Adult , Age Factors , Aged , Alleles , Argentina , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Chile , Female , Humans , Indians, North American , Indians, South American , Isoxazoles/therapeutic use , Leflunomide , Male , Methotrexate/therapeutic use , Mexico , Middle Aged , Peru , Radiography , Sex Factors , Sulfasalazine/therapeutic useABSTRACT
The prevalence of interstitial lung disease in patients with rheumatoid arthritis varies from 10 to 42%. Rheumatoid arthritis patients with interstitial lung disease have three times the risk of death compared with those without the disease. Prognosis seems to be related to the high-resolution computed tomography pattern. Usual interstitial pneumonia pattern, resembling idiopathic pulmonary fibrosis, carries a worse prognosis. Validated strategies to identify different phenotypes and assess the disease activity in rheumatoid arthritis interstitial lung disease are lacking. However, the utilization of high-resolution computed tomography, composed disease activity scores, and anti-citrullinated peptide antibodies titers can help to guide decisions in clinical practice. Mechanisms involved in lung disease may be different from those implicated in joint involvement. This could explain why in a significant proportion of cases, interstitial lung disease does not improve or even worsens with standard therapies used successfully to treat the joint component (e.g. anti- umor necrosis factor agents). In this scenario, a group of drugs that targets the adaptive immune response (e.g. rituximab or abatacept) seems to target more specifically the process that takes place in the lungs. Moreover, the recent emergence of anti-fibrotic drugs, which have already proven effective in idiopathic pulmonary fibrosis, may provide an alternative treatment strategy in rheumatoid arthritis-usual interstitial pneumonia. In this review, we propose a practical approach to the evaluation and therapy of rheumatoid arthritis interstitial lung disease. Validation of strategies directed to assess the activity of lung disease and identify the underlying mechanisms are needed. Clinical trials evaluating a therapeutic approach with specific targets based on the disease phenotype are warranted.
Subject(s)
Arthritis, Rheumatoid/complications , Lung Diseases, Interstitial/etiology , Tomography, X-Ray Computed , Drug Design , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/physiopathology , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Phenotype , Prevalence , PrognosisABSTRACT
OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. We undertook the present work to perform the first genome-wide association study on individuals from the Americas who are enriched for Native American heritage. METHODS: We analyzed 3,710 individuals from the US and 4 countries of Latin America who were diagnosed as having SLE, and healthy controls. Samples were genotyped with HumanOmni1 BeadChip. Data on out-of-study controls genotyped with HumanOmni2.5 were also included. Statistical analyses were performed using SNPtest and SNPGWA. Data were adjusted for genomic control and false discovery rate. Imputation was performed using Impute2 and, for classic HLA alleles, HiBag. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: The IRF5-TNPO3 region showed the strongest association and largest OR for SLE (rs10488631: genomic control-adjusted P [Pgcadj ] = 2.61 × 10(-29), OR 2.12 [95% CI 1.88-2.39]), followed by HLA class II on the DQA2-DQB1 loci (rs9275572: Pgcadj = 1.11 × 10(-16), OR 1.62 [95% CI 1.46-1.80] and rs9271366: Pgcadj = 6.46 × 10(-12), OR 2.06 [95% CI 1.71-2.50]). Other known SLE loci found to be associated in this population were ITGAM, STAT4, TNIP1, NCF2, and IRAK1. We identified a novel locus on 10q24.33 (rs4917385: Pgcadj = 1.39 × 10(-8)) with an expression quantitative trait locus (eQTL) effect (Peqtl = 8.0 × 10(-37) at USMG5/miR1307), and several new suggestive loci. SLE risk loci previously identified in Europeans and Asians were corroborated. Local ancestry estimation showed that the HLA allele risk contribution is of European ancestral origin. Imputation of HLA alleles suggested that autochthonous Native American haplotypes provide protection against development of SLE. CONCLUSION: Our results demonstrate that studying admixed populations provides new insights in the delineation of the genetic architecture that underlies autoimmune and complex diseases.
Subject(s)
American Indian or Alaska Native/genetics , Lupus Erythematosus, Systemic/genetics , Argentina , CD11b Antigen/genetics , Case-Control Studies , Chile , Chromosomes, Human, Pair 10/genetics , DNA-Binding Proteins/genetics , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , HLA-DQ Antigens/genetics , HLA-DQ beta-Chains/genetics , Haplotypes , Humans , Interferon Regulatory Factors , Interleukin-1 Receptor-Associated Kinases/genetics , Male , Mexico , Mitochondrial Proton-Translocating ATPases/genetics , NADPH Oxidases/genetics , Odds Ratio , Peru , Principal Component Analysis , STAT4 Transcription Factor/genetics , United States , White People/genetics , beta KaryopherinsABSTRACT
We retrospectively studied patients with SLE according to ACR criteria, with NL who underwent a repeat renal biopsy from 2005 to 2012. We analyzed the main indications of renal biopsies, the histopathological Class and activity and chronicity changes. RESULTS The total number of patients with NL was 120, of which 18 (15%) patients underwent repeat renal biopsy, 18 had 2 renal biopsies and 6 had 3 biopsies. 3 (16.7%) patients were smokers; 1 (5.6%) had a history of previous DBT, 2 (11.1%) had a history of hypertension; and 3 (16.7%) patients had previous obesity. The duration of SLE was 15 ± 96 months; the time between the 1st and the 2nd biopsy was 45 ± 11 months and the time between the 2nd and 3rd biopsy was 56 ± 12 months. Indications for repeat biopsy were proteinuria in 10 biopsies (41.6%); proteinuria with impaired renal function in 2 biopsies (8.3%); proteinuria with pathological urine sediment in 8 (33.3%); . and pathological proteinuria with pathological urine sediment and impaired renal function in 4 biopsies (16.6%) The most frequent histological changes found between first and repeat biopsies were class IV to class III: 2 (8.2%) ; Class IV to Class IV: 8 (33.3%), class IV to class III + V: 2 (8.2%); class IV to class IV + V 3 (12.5%); class IV to class V: 2 (8.2%). Changes in NL biopsies with proliferative activity and chronicity indices (A / C) were: A to A / C: 7 (29.1%), A / C to A / C: 7 (29.1%). The immunosuppressive therapy was increased in 79.1% and 16.6% remained without changes. 20% patients received cyclophosphamide 1 g every 30 days, 26% Cyclophosphamide 500 mg every 15 days, 23% induction therapy with mycophenolate mofetil; 23% with Rituximab; 8% Cyclosporin A. Maintenance therapy with mycophenolate mofetil was performed in 87.5%; azathioprine in 1 case. Hydroxychloroquine was used in all cases.
Se estudiaron retrospectivamente pacientes con diagnóstico de lupus eritematoso sistémico (LES) de acuerdo a criterios ACR 1982, con nefritis lúpica (NL) durante el período comprendido desde 2005 al 2012 y que fueran sometidos a una biopsia renal repetida. El número total de pacientes con NL atendidos fue de 120, de los cuales 18 (15%) pacientes fueron sometidos a biopsia renal repetida, 18 con 2 biopsias renales y 6 con 3 biopsias. 3 (16,7%) de los pacientes fueron fumadores; 1 (5,6%) poseía antecedentes de DBT previa, 2 (11,1%) poseían antecedentes de HTA; y 3 (16,7%) pacientes tenían obesidad previa. El tiempo de diagnóstico de LES al momento del estudio fue de 96 meses ± 15; el tiempo transcurrido entre la 1° y la 2° biopsia fue de 45 ± 11 meses y el tiempo entre la 2° y 3° biopsia fue de 56 ± 12 meses. Las indicaciones de la biopsia repetida fueron proteinuria en 10 biopsias (41,6%); proteinuria con alteración de la función renal en 2 biopsias (8,3%); proteinuria con sedimento patológico en 8 biopsias (33,3%); y proteinuria con sedimento patológico y alteración de la función renal en 4 biopsias (16,6%). Los cambios histológicos más frecuentes encontrados entre las primeras y las biopsias repetidas fueron: de clase IV a clase III: 2 (8,2%); clase IV a clase IV: 8 (33,3%), clase IV a clase III+V: 2 (8,2%); clase IV a clase IV+V: 3 (12,5%); clase IV a clase V: 2 (8,2%). Los cambios en las biopsias de NL proliferativas con índices de actividad y cronicidad (A/C) fueron: de A a A/C: 7 (29,1%), A/C a A/C: 7 (29,1%). La intensidad de la terapia inmunosupresora aumentó en 79,1%, se mantuvo el tratamiento inmunosupresor en 16.6%. Con respecto al cambio de medicación 7 (20%) pacientes recibieron Ciclofosfamida 1 gr cada 30 días, 9 (26%) Ciclofosfamida 500 mg cada 15 días, 8 (23%) tratamiento de reinducción con Micofenolato mofetil; Rituximab 8 (23%); y 3 (8%) Ciclosporina A. El tratamiento de mantenimiento se realizó con micofenolato mofetil en 23 casos (55%); con azatioprina en 11 (26%) casos; ciclosporina en 3 (7%) oportunidades y rituximab en 5 (12%). En todos los casos se utilizó hidroxicloroquina.
Subject(s)
Kidney/pathology , Lupus Nephritis/pathology , Adult , Antibodies, Antinuclear/blood , Antirheumatic Agents/administration & dosage , Biopsy , Female , Humans , Immunosuppressive Agents/administration & dosage , Lupus Nephritis/drug therapy , Male , Recurrence , Retrospective Studies , Severity of Illness IndexABSTRACT
Para determinar la presencia de debilidad muscular respiratoria asociada a dermatomiositis (DM) su relación con el grado de disnea, actividad de la enfermedad y alteración funcional pulmonar, se evaluó prospectivamente la contractilidad diafragmática en cuatro pacientes con criterios diagnósticos para DM. Dos pacientes tenían disnea y en 3/4 se encontró Incapacidad Ventilatoria Restrictiva. Se descartó obstrucción de la vida aérea y compromiso pulmonar parenquimato. Todos evidenciaron reducción moderada a severa de la presión inspiratoria máxima (Primax) y de la presión diafragmática máxima (Pdimax). Concluimos que todos los pacientes tuvieron debilidad muscular respiratoria que no se correlacionó con la presencia y grado de disnea ni con los parámetros de actividad de la enfermedad. En 3/4 pacientes se pudo demostrar que la Incapacidad Ventilatoria Restrictiva respondía a debilidad muscular respiratoria (AU)
Subject(s)
Male , Female , Adult , Middle Aged , Respiratory Muscles , DermatomyositisABSTRACT
Para determinar la presencia de debilidad muscular respiratoria asociada a dermatomiositis (DM) su relación con el grado de disnea, actividad de la enfermedad y alteración funcional pulmonar, se evaluó prospectivamente la contractilidad diafragmática en cuatro pacientes con criterios diagnósticos para DM. Dos pacientes tenían disnea y en 3/4 se encontró Incapacidad Ventilatoria Restrictiva. Se descartó obstrucción de la vida aérea y compromiso pulmonar parenquimato. Todos evidenciaron reducción moderada a severa de la presión inspiratoria máxima (Primax) y de la presión diafragmática máxima (Pdimax). Concluimos que todos los pacientes tuvieron debilidad muscular respiratoria que no se correlacionó con la presencia y grado de disnea ni con los parámetros de actividad de la enfermedad. En 3/4 pacientes se pudo demostrar que la Incapacidad Ventilatoria Restrictiva respondía a debilidad muscular respiratoria