RESUMEN
Acute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G-coupled receptor FPRL-1. Here we report alternative signaling through the high-density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and -8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA.
Asunto(s)
Artritis Reumatoide/metabolismo , Antígenos CD36/fisiología , Regulación de la Expresión Génica , Inflamación/patología , Proteína Amiloide A Sérica/biosíntesis , Membrana Sinovial/metabolismo , Artroscopía/métodos , Biopsia , Antígenos CD36/metabolismo , Relación Dosis-Respuesta a Droga , Endotelio Vascular/citología , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Péptidos/química , FenotipoRESUMEN
PURPOSE OF REVIEW: Psoriatic arthritis (PsA) is the second most commonly identified inflammatory arthropathy in early arthritis clinics. It is a complex multisystem disease involving the skin and joints, but may also present with inflammation of the spine - spondylitis, digits - dactylitis, eyes - uveitis and ligamentous insertions - enthesitis. The skin manifestations may be mild or patchy and often precede the joint inflammation. Joint erosions, however, may occur within the first 2 years in up to half of PsA patients and an erosion rate of 11% per annum has been reported suggesting it is not a benign disease as it was once regarded. RECENT FINDINGS: Therapy with mild anti-inflammatories is only beneficial in very mild or localized disease. In cases of more widespread joint involvement systemic therapy with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate may be required and in the case of extra-articular or spinal disease, in which DMARDs have failed to show efficacy, biologic therapy may be highly effective. SUMMARY: The question of how early treatment should be instituted should be decided in a specialist rheumatology referral centre following appropriate assessment. Optimal therapy with combination DMARD and biologics may result in remission rates of up to 60%.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Artritis Psoriásica/terapia , Receptores del Factor de Necrosis Tumoral/antagonistas & inhibidores , Antirreumáticos/uso terapéutico , Humanos , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
OBJECTIVES: Pneumococcal and influenza vaccination rates have been suboptimal in studies of immunosuppressed patients. We aimed to assess barriers to and increase rates of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and influenza vaccination in this group. The primary endpoint was a statistically significant increase in adequate PPSV23 and influenza vaccination. METHODS: In 2017, rheumatology outpatients completed an anonymous questionnaire recording vaccination knowledge, status, and barriers. Simultaneously, a low-cost multifaceted quality improvement (QI) intervention was performed. All outpatients on oral steroids, immunosuppressant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologics disease-modifying antirheumatic drugs (bDMARDs) were included in the study. In 2018, post-intervention, the clinic was re-assessed. Demographics, diagnosis, medications, smart phone access, and willingness to use this for vaccination reminders were assessed for independent vaccination predictors using binary logistic regression analysis. RESULTS: Four hundred twenty-five patients were included (72.6% rheumatoid arthritis, 74% women, 45.6% ≥ 60 years old). From 2017 to 2018, PPSV23 vaccination rates changed from 41.0 to 47.2% (P = 0.29) and influenza from 61.8 to 62.1% (P = 0.95). The most common reason for non-vaccination was lack of awareness. Following the intervention, this changed for influenza (36.7 to 34.2%) and PPSV23 (82.1 to 76.4%). General practitioners performed most vaccinations, only 3.6% were delivered in the hospital. Significant predictors of PPSV23 vaccination were older age {≥ 80 years had an OR 41.66 (95% CI 3.69-469.8, P = 0.003), compared with ≤ 39 years}, bDMARD use (OR 2.80, 95% CI 1.24-6.32, P = 0.013), and adequate influenza vaccination (OR 9.01, 95% CI 4.40-18.42, P < 0.001). Up-to-date PPSV23 vaccination (OR 8.93, 95% CI 4.39-18.17, P < 0.001) predicted influenza vaccination. CONCLUSIONS: PPSV23 and influenza vaccination rates were suboptimal. The intervention did not cause a statistically significant change in vaccination rates. Point-of-care vaccination may be more effective.Key Points⢠Low vaccination rates amongst immunosuppressed inflammatory arthritis outpatients⢠Less than 5% of vaccinations occurred in hospital⢠There was no statistically significant difference in the rates of adequate PPSV23 (41.0 to 47.2%) or influenza (61.8 to 62.1%) vaccination following our intervention.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Vacunas contra la Influenza , Vacunas Neumococicas , Mejoramiento de la Calidad/organización & administración , Vacunación/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Antirreumáticos/uso terapéutico , Femenino , Humanos , Huésped Inmunocomprometido , Irlanda , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Rheumatic disease (RD) patients when family planning must consider fertility, disease activity, and management from preconception to lactation. A clear understanding is necessary, especially for those receiving disease-modifying antirheumatic medications. Previous studies have highlighted unmet needs in the care of women with RDs with reproductive healthcare needs. This study describes the first published standardized reproductive care pathway for women with RDs and the outcomes of this approach. MATERIAL AND METHODS: We developed the care pathway with multidisciplinary input from rheumatologists, rheumatology nurse specialists, obstetricians, midwives, maternal medicine specialists, and pharmacists. We identified patients' emotional and healthcare needs, ensured access to expert advice, maintenance of good disease control, and positive reproductive outcomes. We prospectively followed the patients and report the results of the service. RESULTS: Ninety-eight women with median age (range) of 35 years (19-48) were assessed. The majority had an inflammatory arthritis. Seventy-six babies were born to 62 mothers. There were 12 miscarriages and one perinatal death. Breastfeeding rates at 6 weeks were low (28%). CONCLUSION: We describe the first published evidence-based integrated multidisciplinary reproductive care pathway for women with RDs and the results of this approach. Seventy percent of women successful in trying to conceive delivered a healthy baby, and 90% of patients were 'very satisfied' with the service.
Asunto(s)
Fertilidad/fisiología , Enfermedades Reumáticas/complicaciones , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/inmunología , Humanos , Interleucina-12/inmunología , Interleucina-17/inmunología , Interleucina-23/inmunología , Isoxazoles/uso terapéutico , Leflunamida , Metotrexato/uso terapéutico , Transducción de Señal/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , UstekinumabRESUMEN
BACKGROUND: Osteoarthritis (OA) is the most common cause of disability in people older than 65 years. Readability of online OA information has never been assessed. A 2003 study found the quality of online OA information to be poor. OBJECTIVE: The aim of this study was to review the readability and quality of current online information regarding OA. METHODS: The term osteoarthritis was searched across the three most popular English language search engines. The first 25 pages from each search engine were analyzed. Duplicate pages, websites featuring paid advertisements, inaccessible pages (behind a pay wall, not available for geographical reasons), and nontext pages were excluded. Readability was measured using Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. Website quality was scored using the Journal of the American Medical Association (JAMA) benchmark criteria and the DISCERN criteria. Presence or absence of the Health On the Net Foundation Code of Conduct (HONcode) certification, age of content, content producer, and author characteristics were noted. RESULTS: A total of 37 unique websites were found suitable for analysis. Readability varied by assessment tool from 8th to 12th grade level. This compares with the recommended 7th to 8th grade level. Of the 37, 1 (2.7%) website met all 4 JAMA criteria. Mean DISCERN quality of information for OA websites was "fair," compared with the "poor" grading of a 2003 study. HONcode-endorsed websites (43%, 16/37) were of a statistically significant higher quality. CONCLUSIONS: Readability of online health information for OA was either equal to or more difficult than the recommended level.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Evaluación de Resultado en la Atención de Salud , Abatacept , Antirreumáticos/farmacología , Artritis Psoriásica/patología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/patología , Humanos , Inmunoconjugados/farmacología , Imagen por Resonancia Magnética , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
In many ways, it may be easier to highlight what rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have in common. They are both common conditions characterised by a spectrum of features or clinical manifestations in different organ systems that have led many to conclude that they are actually 'disease syndromes'. Furthermore, many of the organ systems that are affected in both conditions are the same: skin, joints, eyes, vasculature and even the immune system. Indeed, some clinicians fail to recognise these two common arthritides as distinct. And yet, while the manifestations may have a superficial similarity, there are significant differences at a number of levels including clinical, anatomical, microscopic and molecular levels. However, these differences may explain certain clinical manifestations of the two diseases, and more importantly, they may explain different responses to specific therapies and potentially different disease outcomes and prognoses. This may be especially relevant as new therapeutic targets are examined that may be specific for RA or PsA.
RESUMEN
Psoriatic arthritis (PsA) is the second most common inflammatory arthropathy, after rheumatoid arthritis diagnosis, in early arthritis clinics. Most patients have established psoriasis, often for years, prior to the onset of joint pain and swelling; in addition, associated features of nail disease, dactylitis, enthesitis, spondylitis or uveitis may be present. Psoriasis may not be immediately apparent, as small or patchy lesions may occur in the scalp or perineum. PsA presents as a symmetrical polyarthritis, similar to rheumatoid arthritis, or an asymmetrical oligoarthritis with a predilection for the distal interphalangeal joints. Spinal involvement is similar, although not identical, to ankylosing spondylitis. Joint damage occurs early; up to 50% of PsA patients have an 11% annual erosion rate in the first 2 years of disease duration, suggesting it is not a benign condition. There have been significant advances in our understanding of PsA pathogenesis in recent years, in the areas of genetics and molecular biology, implicating both the innate and the adaptive immune systems. This has lead to the introduction of evidence-based targeted therapy, primarily with tumour necrosis factor inhibitor (TNFi) agents. Therapy with disease-modifying anti-rheumatic drugs, such as methotrexate and leflunomide, remains the first-choice therapeutic intervention, even though there are few randomised controlled trials with these agents. In contrast, a number of successful studies of TNFi agents demonstrate excellent efficacy, in combination with methotrexate, and several novel agents are currently in development for the treatment of PsA.