Usefulness of Lung Ultrasound as a Method for Early Diagnosis of Interstitial Lung Disease in Patients with Rheumatoid Arthritis.

Purpose: To determine the value of lung ultrasound (LUS) compared to high-resolution computed tomography (HRCT) in the early diagnosis of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Patients and Methods: An observational prospective study was performed. Were included patients with respiratory symptoms or/and, patients with crackles in auscultation during medical consultation. All patients underwent to chest X-rays, LUS, HRCT,and respiratory function tests. Results: A total of 192 patients with RA were included. Mean disease duration was 16.8 ± 11.1 years. 72% were positive for rheumatoid factor or anti-citrullinated antibodies. Of the total number of subjects, 54.7% had respiratory symptoms. The other patients did not have respiratory symptoms, but they did have had crackles on pulmonary auscultation. B lines > 11.5 on the ROC curve predicted ILD (AUC 0.63; CI 95%: 0.55-0.71; p < 0.003). A DLCO value of <7.13 significantly predicted the presence of ILD (AUC 0.61; 95% CI: 0.52-0.70; p < 0.028). Conclusion: The findings of this study suggest that LUS is a valuable tool for the early diagnosis of ILD in patients with RA, and together with DLCO, can adequately predict the presence of ILD in this population. LUS also helps to determine which patients with respiratory symptoms and signs suggestive for ILD are undergo to HRCT.

Design of an algorithm for the diagnostic approach of patients with joint pain.

BACKGROUND: Rheumatic diseases are a reason for frequent consultation with primary care doctors. Unfortunately, there is a high percentage of misdiagnosis. OBJECTIVE: To design an algorithm to be used by primary care physicians to improve the diagnostic approach of the patient with joint pain, and thus improve the diagnostic capacity in four rheumatic diseases. METHODS: Based on the information obtained from a literature review, we identified the main symptoms, signs, and paraclinical tests related to the diagnosis of rheumatoid arthritis, spondyloarthritis with peripheral involvement, systemic lupus erythematosus with joint involvement, and osteoarthritis. We conducted 3 consultations with a group of expert rheumatologists, using the Delphi technique, to design a diagnostic algorithm that has as a starting point "joint pain" as a common symptom for the four diseases. RESULTS: Thirty-nine rheumatologists from 18 countries of Ibero-America participated in the Delphi exercise. In the first consultation, we presented 94 items to the experts (35 symptoms, 31 signs, and 28 paraclinical tests) candidates to be part of the algorithm; 74 items (25 symptoms, 27 signs, and 22 paraclinical tests) were chosen. In the second consultation, the decision nodes of the algorithm were chosen, and in the third, its final structure was defined. The Delphi exercise lasted 8 months; 100% of the experts participated in the three consultations. CONCLUSION: We present an algorithm designed through an international consensus of experts, in which Delphi methodology was used, to support primary care physicians in the clinical approach to patients with joint pain. Key Points • We developed an algorithm with the participation of rheumatologists from 18 countries of Ibero-America, which gives a global vision of the clinical context of the patient with joint pain. • We integrated four rheumatic diseases into one tool with one common symptom: joint pain. It is a novel tool, as it is the first algorithm that will support the primary care physician in the consideration of four different rheumatic diseases. • It will improve the correct diagnosis and reduce the number of paraclinical tests requested by primary care physicians, in the management of patients with joint pain. This point was verified in a recently published study in the journal Rheumatology International (reference number 31).

Reliability of OMERACT ultrasound elementary lesions in gout: results from a multicenter exercise.

The aim of this study was to evaluate the reliability of the outcome measures in rheumatology (OMERACT) definitions for ultrasound (US) elementary lesions in gout through an image reading exercise. Images from patients with gout (static images and videos) were collected. As an initial step, we carried out a image reading exercise within the experts of the Pan-American League of Associations for Rheumatology (PANLAR) US Study Group (n = 16). The following step consisted in a web-based exercise with the participation of larger number of sonographers (n = 63) from different centers. Images were rated evaluating the presence/absence of any US elementary lesion. Inter- and intra-reader reliabilities were analyzed using kappa coefficients. Participants were stratified according to their level of experience. In the first exercise, inter-reader kappa values were 0.45 for aggregates, 0.57 for tophus, 0.69 for erosions, and 0.90 for double contour (DC). Intra-reader kappa values were 0.86, 0.76, 0.80, and 0.90, respectively. The web-based exercise showed inter-reader kappa values for aggregates, tophus, erosions, and DC of 0.42, 0.49, 0.69, and 0.79, respectively. The intra-reader kappa values were 0.62, 0.69, 0.77, and 0.85, respectively. Reliability was not influenced by the sonographer's level of experience. The reliability of the new OMERACT US definitions for elementary lesions in gout ranged from moderate to excellent, depending on the type of lesion.

How is the ultrasound in rheumatology used, implemented, and applied in Latin American centers? Results from a multicenter study.

This study aimed to perform an overview of how ultrasound (US) is being used, implemented, and applied in rheumatologic centers in Latin America (LA). A retrospective, multicenter 1-year experience study was undertaken. Eighteen centers from eight countries were involved. The following information were collected: demographic data, indication to perform an US examination, physician that required the examination, and the anatomical region required for the examination. A total of 7167 patients underwent an US examination. The request for US examinations came most frequently from their own institution (5981 (83.45 %)) than from external referral (1186 (16.55 %)). The services that more frequently requested an US examination were rheumatology 5154 (71.91 %), followed by orthopedic 1016 (14.18 %), and rehabilitation 375 (5.23 %). The most frequently scanned area was the shoulder in 1908 cases (26.62 %), followed by hand 1754 (24.47 %), knee 1518 (21.18 %), ankle 574 (8.01 %), and wrist 394 (5.50 %). Osteoarthritis was the most common disease assessed (2279 patients (31.8 %)), followed by rheumatoid arthritis (2125 patients (29.65 %)), psoriatic arthritis (869 patients (12.1 %)), painful shoulder syndrome (545 (7.6 %)), connective tissue disorders (systemic sclerosis 339 (4.7 %), polymyositis/dermatomyositis 107 (1.4 %), Sjögren's syndrome 60 (0.8 %), and systemic lupus erythematosus 57 (0.8 %)). US evaluation was more frequently requested for diagnostic purposes (3981 (55.5 %)) compared to follow-up studies (2649 (36.9 %)), research protocols (339 (4.73 %)), and invasive guided procedures (198 (2.76 %)). US registered increasing applications in rheumatology and highlighted its positive impact in daily clinical practice. US increases the accuracy of the musculoskeletal clinical examination, influence the diagnosis, and the disease management.

La ultrasonografía en el estudio de rodilla dolorosa / Ultrasonography in the study of painful knee

La presencia de dolor y/o tumefacción a nivel de la rodilla es un motivo de consulta frecuente, ya sea en pacientes con enfermedad reumatológica definida o en la población general. Si bien la rodilla es una región accesible para el examen clínico, la ultrasonografía se ha convertido en una herramienta de gran ayuda para el reumatólogo al momento de definir el origen del dolor y/o la tumefacción, ya que permite detectar inclusive mínimas alteraciones morfoestructurales a nivel de las distintas estructuras anatómicas de la rodilla. En la práctica clínica es importante destacar la importancia de la ultrasonografía para la detección de sinovitis y entesopatía subclínicas en las artropatías inflamatorias, así como para demostrar cambios mínimos sugestivos de artropatía degenerativa y microcristalina. Por otra parte, esta técnica es de suma utilidad en la determinación del origen de los distintos síndromes regionales dolorosos y es una herramienta eficaz como guía para el intervencionismo diagnóstico y/o terapéutico. La ultrasonografía cuenta con muchas ventajas, tales como la inocuidad, el bajo costo operativo y la posibilidad de estudiar múltiples regiones en tiempo real y dinámico; sin embargo, en la actualidad, la larga curva de aprendizaje quizás sea una de sus mayores limitaciones.

The presence of knee pain and/or swelling is an important reason of attendance in rheumatologic daily practice. Although knee is an accessible region to be evaluated by the physical examination ultrasonography has been converted in an excellent and helping tool for the rheumatologists in order to establish the origin of the knee pain and/or swelling. Ultrasonography has the ability to detect subclinical synovitis and enthesopathy in patients with inflammatory arthritis and to demonstrate minimal changes indicative of degenerative or mycrocristaline arthropathies. Moreover, ultrasonography can be useful to determinate the cause of the different pain regional syndromes and is a very good option to be used as guide for the interventional arthrocentesis. Ultrasonography has several advantages as safety, low cost and the capability to study many joints in a realtime. However, at the present the large learning curve might be one of the main limitations.

Pan-American League of Associations for Rheumatology (PANLAR) recommendations and guidelines for musculoskeletal ultrasound training in the Americas for rheumatologists.

OBJECTIVE: To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the Americas. METHODS: A total of 25 Rheumatologists from 19 countries of the American Continent participated in a consensus-based interactive process (Delphi method) using 2 consecutive electronic questionnaires. The first questionnaire included the following: the relevance of organizing courses to teach MSKUS to Rheumatologists, the determination of the most effective educational course models, the trainee levels, the educational objectives, the requirements for passing the course(s), the course venues, the number of course participants per instructor, and the percentage of time spent in hands-on sessions. The second questionnaire consisted of questions that did not achieve consensus (>65%) in the first questionnaire, topics, and pathologies to be covered at each course MSKUS level. RESULTS: General consensus was obtained for MSKUS courses to be divided into 3 educational levels: basic, intermediate, and advanced. These courses should be taught using a theoretical-didactic and hands-on model. In addition, the group established the minimum requirements for attending and passing each MSKUS course level, the ideal number of course participants per instructor (4 participants/instructor), and the specific topics and musculoskeletal pathologies to be covered. In the same manner, the group concluded that 60% to 70% of course time should be focused on hands-on sessions. CONCLUSION: A multinational group of MSKUS sonographers using a consensus-based questionnaire (Delphi method) established the first recommendations and guidelines for MSKUS course training in the Americas. Pan-American League of Associations for Rheumatology urges that these guidelines and recommendations be adopted in the future by both national and regional institutions in the American continent involved in the training of Rheumatologists for the performance of MSKUS.

Do arachidonic acid and its metabolites, secreted by rheumatoid and osteoarthritic synovial tissue, account for the strong inhibition of DNA synthesis in cultured human articular chondrocytes? A novel approach to the mechanism of tissue damage.

AIMS: To further characterize factors secreted in vitro by osteoarthritic and rheumatoid arthritis synovial membranes that inhibit DNA synthesis by cultured human articular chondrocytes, and extend these findings to synovial fluid. MATERIAL AND METHODS: Synovial tissue, synovial fluid and articular cartilage were obtained at surgery from two patients suffering rheumatoid arthritis and two other patients suffering from osteoarthritis. Synovial tissue was incubated in DMEM, then condition media and synovial fluids were extracted with methanol. Methanol extracts and extracted residues (hyaluronic acid, proteins) were assayed for their capacity to inhibit DNA synthesis in articular chondrocytes. Methanol extracts were also fractionated by thin layer chromatography on silica-coated plates and recovered fractions similarly tested. RESULTS: All extracts exhibited strong and concentration-dependent inhibition of [3H]-thymidine incorporation. The most potent inhibition was obtained with the extracts from rheumatoid joints and the least potent inhibition was with synovial fluids. The removal of active substances with methanol leaves an inactive residue. Methanol extraction does not alter the mitogenic activity of five exogenous growth factors and two cytokines, thus suggesting that such activity is entirely due to lipids. The bulk of anti-mitotic factors extracted by methanol co-migrate when fractionated by thin layer chromatography on silica-coated plates with arachidonic acid and its lipo-oxygenase metabolites. IN CONCLUSION: Inflamed synovium produces and releases lipids, most probably arachidonic acid metabolites that inhibit cell proliferation thus limiting inflammation and pannus formation in arthritis.

Variability in the cell phenotype of aggregates or "clones" of human osteoarthritic cartilage. A case report

Human samples of articular cartilage from the knee of a clinically classified osteoarthritic patient, assessed by arthroscopy as part of the surgical treatment was studied by light and transmission electron microscopy. This particular case differed from others already reported in the variability of cell phenotype within the aggregates or "clones" frequently present in the osteoarthritic cartilage. The most common morphology of "clonal" cells forming the aggregates were large and rounded with an euchromatic nucleus. The cytoplasm was characterized by the presence of alternately clear and dense sites. At the ultrastructural level it was seen that the clear sites were formed by disrupted intermediates filaments and small particles, and that the dense sites were constituted by the segregation of different organelles of the chondrocytes. In addition, there were atypical aggregates composed only by secretory cells or by degenerating chondrocytes. Furthermore, a complex structure consisting of a very large cell inside a giant lacunae delimited by electron-dense material with small vesicles is described as a novel finding. The variability in the chondrocyte phenotype of the aggregates described here could be an indication of a better prognosis; nevertheless, the follow-up of the evolution of this patient is needed in order to know the final outcome.(AU)

Variability in the cell phenotype of aggregates or "clones" of human osteoarthritic cartilage. A case report

Human samples of articular cartilage from the knee of a clinically classified osteoarthritic patient, assessed by arthroscopy as part of the surgical treatment was studied by light and transmission electron microscopy. This particular case differed from others already reported in the variability of cell phenotype within the aggregates or "clones" frequently present in the osteoarthritic cartilage. The most common morphology of "clonal" cells forming the aggregates were large and rounded with an euchromatic nucleus. The cytoplasm was characterized by the presence of alternately clear and dense sites. At the ultrastructural level it was seen that the clear sites were formed by disrupted intermediates filaments and small particles, and that the dense sites were constituted by the segregation of different organelles of the chondrocytes. In addition, there were atypical aggregates composed only by secretory cells or by degenerating chondrocytes. Furthermore, a complex structure consisting of a very large cell inside a giant lacunae delimited by electron-dense material with small vesicles is described as a novel finding. The variability in the chondrocyte phenotype of the aggregates described here could be an indication of a better prognosis; nevertheless, the follow-up of the evolution of this patient is needed in order to know the final outcome.

Nuevos conceptos en la etiopatogenia de la artrosis / New concepts in the etiopatogenic of the osteoarthritis

Son múltiples los agentes nocivos que pueden desencadenar una lesión artrósica, pero no en forma aislada y sin un terreno que predisponga al paciente. Sin embargo, nuestros estudios estructurales del cartílago indican que el centro de la lesión artrósica es el condrocito, y que independientemente de cuáles sean los factores etiopatogénicos, debe ocurrir una alteración de la interfase hueso-cartílago para que se produzcan daños en este tejido, y se altere, rompiéndose el equilibrio cuya consecuencia son las alteraciones descritas