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1.
Nat Commun ; 14(1): 319, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658110

RESUMO

The immune mechanisms that mediate synovitis and joint destruction in rheumatoid arthritis (RA) remain poorly defined. Although increased levels of CD8+ T cells have been described in RA, their function in pathogenesis remains unclear. Here we perform single cell transcriptome and T cell receptor (TCR) sequencing of CD8+ T cells derived from anti-citrullinated protein antibodies (ACPA)+ RA blood. We identify GZMB+CD8+ subpopulations containing large clonal lineage expansions that express cytotoxic and tissue homing transcriptional programs, while a GZMK+CD8+ memory subpopulation comprises smaller clonal expansions that express effector T cell transcriptional programs. We demonstrate RA citrullinated autoantigens presented by MHC class I activate RA blood-derived GZMB+CD8+ T cells to expand, express cytotoxic mediators, and mediate killing of target cells. We also demonstrate that these clonally expanded GZMB+CD8+ cells are present in RA synovium. These findings suggest that cytotoxic CD8+ T cells targeting citrullinated antigens contribute to synovitis and joint tissue destruction in ACPA+ RA.


Assuntos
Artrite Reumatoide , Sinovite , Humanos , Linfócitos T CD8-Positivos/metabolismo , Membrana Sinovial/metabolismo , Receptores de Antígenos de Linfócitos T , Autoantígenos , Autoanticorpos
2.
Am Fam Physician ; 107(1): 42-51, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36689970

RESUMO

Polyarticular joint pain involves five or more joints and can be inflammatory or noninflammatory. Two of the most common causes of chronic polyarthritis are osteoarthritis, especially in older patients, and rheumatoid arthritis, which affects at least 0.25% of adults worldwide. The initial evaluation should include a detailed history of the patient's symptoms, with a focus on inflammation, location of pain, duration of symptoms, the presence of systemic symptoms, and any exposures to pathogens that could cause arthritis. Redness, warmth, or swelling in a joint is suggestive of synovitis and joint inflammation. A systematic approach to the physical examination that assesses for a pattern of joint involvement and presence of synovitis can help narrow the differential diagnosis. Laboratory tests, joint aspiration, and imaging studies should be used to confirm a suspected diagnosis. Rheumatoid factor and cyclic citrullinated peptide antibody tests are helpful when there is concern for rheumatoid arthritis. Although magnetic resonance imaging is highly sensitive in identifying erosive bony changes and inflammation, conventional radiography remains the standard for the initial imaging evaluation of rheumatoid arthritis. Point-of-care musculoskeletal ultrasonography can also be a useful tool to detect findings that support a diagnosis of inflammatory arthritis.


Assuntos
Artrite Reumatoide , Sinovite , Humanos , Adulto , Idoso , Diagnóstico Diferencial , Artrite Reumatoide/diagnóstico , Sinovite/diagnóstico , Sinovite/patologia , Inflamação , Imageamento por Ressonância Magnética/métodos , Artralgia/diagnóstico
3.
Pediatr Rheumatol Online J ; 21(1): 7, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36691078

RESUMO

BACKGROUND: Dry synovitis (DS) is a rare entity as only a few cases have been reported to date. We describe the clinical features, radiological manifestations and course of DS in comparison with rheumatoid factor negative polyarticular juvenile idiopathic arthritis (RFneg-polyJIA). METHODS: We performed a multicenter retrospective collection of data of DS patients who presented with progressive joint limitations without palpable synovitis, absence of elevated acute phase reactants, negative ANA and RF, and imaging showing joint and/or osteochondral involvement. For comparative purposes, we included a cohort of RF neg-polyJIA patients. RESULTS: Twelve DS patients, 8F/4 M, with mean age at onset of 6.1 years, were included. Presenting signs comprised delayed motor development, functional limitations and/or progressive stiffness. Clinical examination showed symmetric polyarticular involvement with variable muscular atrophy. MRI showed mild, diffuse synovial involvement, without effusion. With time, signs of progressive osteochondral damage became evident, despite treatment. All patients were treated with low-dose corticosteroids and methotrexate. Anti-TNF agents were prescribed in five. The response was variable with limited joint mobility in 11/12, and need of joint replacement in 2. In comparison with a cohort of RFneg-polyJIA, DS patients presented higher number of joint involved (p = 0.0001) and contractures (p = 0.0001), less swelling (p = 0.0001) and prolonged diagnostic delay (p = 0.0001). CONCLUSION: DS represents a unique juvenile-onset arthropathy, distinct from polyarticular JIA. Awareness among pediatricians is essential for early recognition and proper treatment. Further studies, including synovial pathology, immunology and genetics may contribute to a better understanding of this rare disorder of childhood.


Assuntos
Artrite Juvenil , Sinovite , Humanos , Criança , Artrite Juvenil/diagnóstico , Estudos Retrospectivos , Diagnóstico Tardio , Inibidores do Fator de Necrose Tumoral , Sinovite/diagnóstico
4.
Trials ; 24(1): 6, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597103

RESUMO

BACKGROUND: Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. METHODS: GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher's exact test). DISCUSSION: GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk-benefit profile of this treatment in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT05291650. Registered on 23 March 2022.


Assuntos
Osteoartrite do Joelho , Sinovite , Humanos , Osteoartrite do Joelho/terapia , Glucocorticoides/efeitos adversos , Qualidade de Vida , Dor/tratamento farmacológico , Injeções Intra-Articulares , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Sinovite/complicações , Inflamação/tratamento farmacológico , Tecido Adiposo , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
5.
Egypt J Immunol ; 30(1): 20-30, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36588450

RESUMO

Rheumatoid arthritis (RA) is characterized by ongoing joint destruction. MicroRNAs (miRs) are blood-based biomarkers linked to RA pathogenesis. The musculoskeletal ultrasonography seven-joint score (US7) is an objective tool to assess RA activity. We aimed to evaluate miR-223 and miR-16 roles in monitoring RA activity and to investigate if there is a link between their plasma levels and US7 score. This study enrolled 76 RA patients classified according to Disease Activity Score 28-joint count with erythrocyte sediment rate (DAS28-ESR) to inactive cases (n = 38) and active cases (n = 38). Each patient's joint was scored for synovial proliferation (gray-scale ultrasound 'GSUS7') and vascularization (power Doppler ultrasound 'PDUS7'). Real-time quantitative PCR was used to measure the expression levels of miR-16 and miR-223 in plasma. When compared to inactive group, the active group revealed significant upregulation of miR-16 and miR-223, (P = 0.001 and P = 0.02, respectively). miR-16 and miR-223 levels were correlated with synovitis PDUS7 (r = 0.34, p < 0.01 and r= 0.25, P = 0.03, respectively). miR-16 was also positively correlated with synovitis GSUS7 (r= 0.42, p < 0.001). miR-223 upregulation discriminated active from inactive RA patients at AUC = 0.64, with 76% sensitivity and 50% specificity at cutoff > 2.8-fold change), whereas miR-16 distinguished the two groups at AUC = 0.78 with 87% sensitivity and 53% specificity at cutoff >38.27-fold change. In conclusion, upregulated miR-16 may have more potential to serve as activity biomarkers than miR-223 in RA. The miR-16 level was linked to synovitis GSUS7 and synovitis PDUS7 changes but miR-223 only linked to synovitis PDUS.


Assuntos
Artrite Reumatoide , MicroRNAs , Sinovite , Humanos , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/genética , Ultrassonografia , Sinovite/diagnóstico por imagem , Sinovite/genética , MicroRNAs/genética , Biomarcadores
6.
Arthritis Res Ther ; 25(1): 7, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635774

RESUMO

BACKGROUND: Hypertension is a common comorbidity of osteoarthritis (OA) with known autonomic dysregulation; thus, the autonomic nervous system may provide a shared underlying mechanism. The objective of this study was to examine the role of the autonomic nervous system in a preclinical model of OA and hypertension. METHODS: Experiments were conducted in spontaneously hypertensive rats and a normotensive control strain, including male and female rats. OA was surgically induced via medial meniscus transection with skin incision used as a sham control (n = 7-8/strain/sex/surgery). Tactile sensitivity, anxiety-related behavior, and serum corticosterone were measured at baseline then bi-weekly across 8 weeks. At weeks 9-10, cardiovascular responses to a chemical vagal nerve agonist were determined to indirectly evaluate vagus nerve function. The joint structure was assessed via grading of histological sections. RESULTS: In males, OA resulted in thinner cartilage in both hypertensive (OA vs. non-OA p < 0.001) and normotensive (OA vs. non-OA p < 0.001). Only females with comorbid hypertension and OA displayed thinner cartilage (p = 0.013). Male hypertensive OA animals had increased calcified subchondral bone compared to normotensive OA animals (p = 0.043) while female hypertensive OA animals had increased calcified subchondral bone compared to hypertensive sham animals (p < 0.001). All MCLT+MMT groups developed low-grade synovitis; interestingly, hypertensive OA females had higher synovitis scores than normotensive OA females (p = 0.046). Additionally, hypertension led to larger drops in blood pressure with vagal activation in both OA (hypertensive vs. normotensive p = 0.018) and sham (hypertensive vs. normotensive p < 0.001) male animals. In females, this trend held true only in OA animals (normotensive vs. hypertensive p = 0.005). CONCLUSION: These data provide preliminary evidence that hypertension influences OA progression and encourages further study into the autonomic nervous system as a possible mechanism.


Assuntos
Cartilagem Articular , Hipertensão , Osteoartrite , Sinovite , Ratos , Masculino , Feminino , Animais , Osteoartrite/patologia , Meniscos Tibiais , Osso e Ossos , Sinovite/patologia , Modelos Animais de Doenças , Cartilagem Articular/patologia
7.
Phytomedicine ; 109: 154616, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610110

RESUMO

BACKGROUND: Curcuma longa (CL) extract is modestly effective for relieving knee symptoms in knee osteoarthritis (OA) patients; however, its mechanism of action is unclear. PURPOSE: We aimed to determine the effects of CL treatment on serum inflammatory markers over 12 weeks and to explore its potential effects on synovitis assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of the knee. METHODS: Secondary analyses were conducted on the CL for knee OA (CurKOA) trial, which compared CL (n = 36) and placebo (n = 34) over 12 weeks for the treatment of knee OA. Systemic inflammatory markers (TNFα, IL6, and hsCRP) and a cartilage extracellular matrix degradative enzyme (MMP-3) were measured. A subgroup of participants (CL, n = 7; placebo, n = 5) underwent CE-MRI at baseline and a 12-week follow-up. RESULTS: Over 12 weeks, there were no between-group differences in change in hsCRP, IL-6, and TNFα levels. MMP-3 levels decreased in both CL (-1.31 ng/ml [95%CI: -1.89 to -0.73]) and placebo (-2.34 ng/ml [95%CI: -2.95 to -1.73]) groups, with the placebo group having a slightly greater decrease (1.03 ng/ml [95%CI: 0.19 to 1.88]). Most (10 of 12) sub-study participants had normal synovial thickness scores at baseline. One participant had mild synovitis in each of the placebo and CL groups. Synovitis status was stable for all except two participants, one each in the CL and placebo group, whose synovitis score increased. CONCLUSION: This is the first study that explored the effect of CL treatment on local and systemic inflammation using biochemical markers and CE-MRI outcomes on knee OA patients. Secondary analyses from this pilot study suggest that CL is unlikely to have clinically significant effects on systemic (inflammatory and cartilage) or local synovitis (CE-MRI) biomarkers compared to placebo. The mechanism of action for CL effect on pain remains unclear.


Assuntos
Osteoartrite do Joelho , Sinovite , Humanos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/tratamento farmacológico , Curcuma , Metaloproteinase 3 da Matriz , Fator de Necrose Tumoral alfa , Proteína C-Reativa/uso terapêutico , Projetos Piloto , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Sinovite/complicações , Biomarcadores , Imageamento por Ressonância Magnética/métodos
8.
BMC Musculoskelet Disord ; 24(1): 23, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631793

RESUMO

BACKGROUND: Undifferentiated arthritis is a condition in which the problem cannot be classified into any definite diagnosis category. Various methods have been suggested to clarify the definite diagnosis in this class. The synovial biopsy is suggested as the last diagnostic approach to determine the precise histopathological diagnosis. In this study, we aimed to evaluate the efficacy of synovial biopsy for establishing a definite diagnosis in patients with undifferentiated chronic knee monoarthritis. METHODS: The present retrospective case series was conducted in 2005 in the rheumatology research center of Shariati hospital and the 501 hospital in Tehran, Iran. The study included the synovial biopsy of patients with chronic knee monoarthritis who did not have a definite diagnosis after all the diagnostic steps before the synovial biopsy. Pathology slides of the patients' synovial biopsy were reevaluated with a senior expert pathologist. RESULTS: Eighty patients with a mean age of 37.6 ± 17.32 years (range: 6-68) were included, of whom 50% were female. The gap time between the onset of knee monoarthritis and the decision-making for synovial biopsy was 14.34 ± 19.61 months. Histopathologic evaluations revealed non-specific synovitis in 65% of the patients and a definite diagnosis in 35%. The most common definite diagnosis was rheumatoid arthritis (9%), followed by septic arthritis (5%). The most common pathologic findings were endothelial proliferation (89%) and synovial proliferation (88%), and the most common infiltrating cell was lymphocyte (54%). Patients with non-specific synovitis were more likely to have neovascularization, cellular infiltration (p-value < 0.001), synovial proliferation, endothelial proliferation (p-value = 0.001), pannus formation (p-value = 0.009), and fibrosis (p-value = 0.022) compared to the patients with a definite pathologic diagnosis. However, age, gender, and the gap time between disease symptoms to synovial biopsy were not significantly different between the different groups of diagnosis (p-value > 0.05). CONCLUSION: Non-specific synovitis remains the most common histopathologic finding, highlighting the importance of physician expert opinion for most of the patients with undifferentiated chronic knee monoarthritis. Studies with larger samples and immunohistochemistry analyses are needed to clarify this uncategorized entity further.


Assuntos
Artrite Reumatoide , Sinovite , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Irã (Geográfico) , Sinovite/diagnóstico , Sinovite/patologia , Artrite Reumatoide/patologia , Biópsia , Articulação do Joelho/patologia , Membrana Sinovial/patologia
9.
PLoS Negl Trop Dis ; 17(1): e0011037, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36608155

RESUMO

BACKGROUND: Chikungunya-fever (CHIKF) remains a public health major issue. It is clinically divided into three phases: acute, post-acute and chronic. Chronic cases correspond to 25-40% individuals and, though most of them are characterized by long-lasting arthralgia alone, many of them exhibit persistent or recurrent inflammatory signs that define post-Chikungunya chronic inflammatory joint disease (pCHIKV-CIJD). We aimed to identify early clinical markers of evolution to pCHIKV-CIJD during acute and post-acute phases. METHODOLOGY/PRINCIPAL FINDINGS: We studied a prospective cohort of CHIKF-confirmed volunteers with longitudinal clinical data collection from symptoms onset up to 90 days, including a 21-day visit (D21). Of 169 patients with CHIKF, 86 (50.9%) completed the follow-up, from whom 39 met clinical criteria for pCHIKV-CIJD (45.3%). The relative risk of chronification was higher in women compared to men (RR = 1.52; 95% CI = 1.15-1.99; FDR = 0.03). None of the symptoms or signs presented at D0 behaved as an early predictor of pCHIKV-CIJD, while being symptomatic at D21 was a risk factor for chronification (RR = 1.31; 95% CI = 1.09-1.55; FDR = 0.03). Significance was also observed for joint pain (RR = 1.35; 95% CI = 1.12-1.61; FDR = 0.02), reported edema (RR = 3.61; 95% CI = 1.44-9.06; FDR = 0.03), reported hand and/or feet small joints edema (RR = 4.22; 95% CI = 1.51-11.78; FDR = 0.02), and peri-articular edema observed during physical examination (RR = 2.89; 95% CI = 1.58-5.28; FDR = 0.002). Furthermore, patients with no findings in physical examination at D21 were at lower risk of chronic evolution (RR = 0.41, 95% CI = 0.24-0.70, FDR = 0.01). Twenty-nine pCHIKV-CIJD patients had abnormal articular ultrasonography (90.6% of the examined). The most common findings were synovitis (65.5%) and joint effusion (58.6%). CONCLUSION: This cohort has provided important insights into the prognostic evaluation of CHIKF. Symptomatic sub-acute disease is a relevant predictor of evolution to chronic arthritis with synovitis, drawing attention to joint pain, edema, multiple articular involvement including small hand and feet joints as risk factors for chronification beyond three months, especially in women. Future studies are needed to accomplish the identification of accurate and early biomarkers of poor clinical prognosis, which would allow better understanding of the disease's evolution and improve patients' management, modifying CHIKF burden on global public health.


Assuntos
Artrite , Febre de Chikungunya , Sinovite , Masculino , Humanos , Feminino , Febre de Chikungunya/complicações , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Estudos Prospectivos , Brasil/epidemiologia , Artralgia/epidemiologia , Artralgia/etiologia , Biomarcadores , Doença Crônica
10.
J Clin Rheumatol ; 29(1): e1-e2, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36544255

RESUMO

ABSTRACT: Intra-articular osteoid osteoma may simulate arthritis, due to the intra-articular presence of prostaglandin, which leads to synovitis, joint effusion, pain, and high local temperature. Also, intra-articular osteoid osteoma may present with minimum or no cortical thickening. Therefore, a high suspicion is needed for a correct and early diagnosis. Perfusion weighted imaging, such as dynamic contrast-enhanced imaging, can aid in the localization of the tumor nidus, seen as an early arterial-phase focal enhancement after the gadolinium injection, with fast washout, as a result of its hypervascularity.


Assuntos
Artrite , Neoplasias Ósseas , Osteoma Osteoide , Sinovite , Humanos , Neoplasias Ósseas/diagnóstico , Osteoma Osteoide/diagnóstico , Tomografia Computadorizada por Raios X , Artrite/diagnóstico , Artrite/etiologia
11.
Pathol Res Pract ; 241: 154273, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36563558

RESUMO

OBJECTIVES: The aim of the present study was to propose a methodologically innovative sonographic approach for optimal evaluation of synovial tissues (starting from histopathology). METHODS: Using high-frequency ultrasound probes and high-level ultrasound machines, we matched the histological microarchitecture of synovial tissues with multiple sonographic patterns in physiological and pathological conditions. Likewise, high-sensitive color/power Doppler assessments have also been performed to evaluate the microcirculation. RESULTS: Modern equipment allows for a macroscopic classification of synovial pathologies recognizing different morphological patterns; however, intimal and subintimal layers of the synovium cannot be distinguished from each other on ultrasound. High-sensitive Doppler imaging clearly defines the microvascular pattern, especially in patients with hypertrophic synovial pathologies. CONCLUSIONS: In clinical practice, using adequate technological equipment i.e. high-frequency B-mode and high-sensitive Doppler imaging, detailed sonographic assessment of synovial tissues can be performed - defining the main sono-histological patterns.


Assuntos
Artrite Reumatoide , Sinovite , Humanos , Artrite Reumatoide/patologia , Sinovite/diagnóstico por imagem , Sinovite/patologia , Ultrassonografia , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/irrigação sanguínea , Membrana Sinovial/patologia , Músculos/patologia
12.
Mediators Inflamm ; 2022: 2581151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466156

RESUMO

The mechanism of temporomandibular joint osteoarthritis (TMJOA), which leads to the final erosion of cartilage and subchondral bone, has been widely demonstrated, but still not clearly elucidated. Many studies have pointed that NLRP3-mediated inflammation played a vital role in degenerative diseases. However, its interaction with synovitis of TMJOA has remained poorly investigated. In our study, we explored the role of NLRP3 inflammasome in TMJOA synovitis and the therapeutic potential of caspase-1 and NLRP3 inhibitors. By establishing a rat TMJOA model, we found that NLRP3 was upregulated in synovial tissue of TMJOA. It was involved in the progress of a programmed cell death called pyroptosis, which was caspase-1 dependent and ultimately triggered inflammatory mediator interleukin IL-1ß release. Treatment with Ac-YVAD-cmk and MCC950, inhibitors targeting caspase-1 and NLRP3, respectively, significantly suppressed pyroptosis in TMJOA synovial tissue. Then, a macrophage- and fibroblast-like synoviocyte (FLS) cocultured model further verified the above results. Macrophage somehow promoted FLS pyroptosis in this study. Our results suggested that the NLRP3 inflammasome-mediated pyroptosis participated in synovial inflammation of TMJOA. Interfering with the progress could be a potential option for controlling TMJOA development.


Assuntos
Osteoartrite , Sinovite , Ratos , Animais , Piroptose , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Articulação Temporomandibular , Sinovite/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Caspase 1 , Inflamação/tratamento farmacológico
14.
BMC Vet Res ; 18(1): 436, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36514067

RESUMO

BACKGROUND: Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. Secondarily, pharmacodynamic effects, including effects on joint circumference, joint flexion, and lameness following intra-articular administration of isoflupredone acetate in the experimental model were described. METHODS: Sixteen horses received a single intra-articular dose of 8 mg of isoflupredone acetate or saline 12 h post-administration of lipopolysaccharide. Blood and urine samples were collected up to 72 h and synovial fluid for 28 days post-administration, drug concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Joint circumference, maximum angle of pain free joint flexion and lameness were evaluated prior to and post-treatment. RESULTS: The maximum isoflupredone plasma concentration was 2.45 ± 0.61 ng/mL at 2.5 ± 0.75 h and concentrations were less than the limit of quantitation by 72 h. Isoflupredone was below detectable concentrations in urine by 72 h post-administration in all horses and no longer detectable in synovial fluid by 96 h post-administration. Joint circumference was significantly decreased in the isoflupredone treatment group compared to the saline group at 24 and 48 h post drug administration. Pain free joint flexion was significantly different between the saline and isoflupredone treatment groups on day 4 post-treatment. CONCLUSIONS: Synovial fluid concentrations and maximum plasma concentrations of isoflupredone differed slightly between the current study and a previous one describing administration into a non-inflamed joint, however, the detection time of isoflupredone in blood was comparable. Effects of isoflupredone on joint circumference and degree of pain free joint flexion suggest a short duration of effect with respect to alleviation of lipopolysaccharide induced synovitis, however, results of this study support future studies of the anti-inflammatory effects of intra-articular isoflupredone acetate.


Assuntos
Doenças dos Cavalos , Sinovite , Cavalos , Animais , Lipopolissacarídeos , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/tratamento farmacológico , Injeções Intra-Articulares/veterinária , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico , Sinovite/veterinária , Líquido Sinovial , Inflamação/tratamento farmacológico , Inflamação/veterinária , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/tratamento farmacológico
15.
RMD Open ; 8(2)2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36549857

RESUMO

OBJECTIVE: To identify predictors of flare in a 2-year follow-up study of patients with rheumatoid arthritis (RA) in sustained clinical remission tapering towards withdrawal of biological disease-modifying anti-rheumatic drugs (bDMARDs). METHODS: Sustained clinical remission was defined as Disease Activity Score for 28 joints (DAS28)-C reactive protein (CRP) ≤2.6 without radiographic progression for >1 year. bDMARDs were tapered according to a mandatory clinical guideline to two-thirds of standard dose at baseline, half of dose at week 16 and discontinuation at week 32. Prospective assessments for 2 years included clinical evaluation, conventional radiography, ultrasound and MRI for signs of inflammation and bone changes. Flare was defined as DAS28-CRP ≥2.6 with ∆DAS28-CRP ≥1.2 from baseline. Baseline predictors of flare were assessed by logistic regression analyses. RESULTS: Of 142 included patients, 121 (85%) flared during follow-up of which 86% regained remission within 24 weeks after flare. Patients that flared were more often rheumatoid factor positive, had tried more bDMARDs and had higher baseline ultrasound synovitis sum scores than those not flaring. For patients on standard dose, predictors of flare within 16 weeks after reduction to two-thirds of standard dose were baseline MRI-osteitis (OR 1.16; 95% CI 1.03 to 1.33; p=0.014), gender (female) (OR 6.71; 95% CI 1.68 to 46.12; p=0.005) and disease duration (OR 1.06; 95% CI 1.01 to 1.11; p=0.020). Baseline predictors for flare within 2 years were ultrasound grey scale synovitis sum score (OR 1.19; 95% CI 1.02 to 1.44; p=0.020) and number of previous bDMARDs (OR 4.07; 95% CI 1.35 to 24.72; p=0.007). CONCLUSION: The majority of real-world patients with RA tapering bDMARDs flared during tapering, with the majority regaining remission after stepwise dose increase. Demographic and imaging parameters (MR-osteitis/ultrasound greyscale synovitis) were independent predictors of immediate flare and flare overall and may be of importance for clinical decision-making in patients eligible for tapering.


Assuntos
Antirreumáticos , Artrite Reumatoide , Osteíte , Sinovite , Humanos , Feminino , Seguimentos , Osteíte/tratamento farmacológico , Estudos Prospectivos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico
16.
Immunity ; 55(12): 2255-2270, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36516818

RESUMO

Significant recent progress in understanding rheumatoid arthritis (RA) pathogenesis has led to improved treatment and quality of life. The introduction of targeted-biologic and -synthetic disease modifying anti-rheumatic drugs (DMARDs) has also transformed clinical outcomes. Despite this, RA remains a life-long disease without a cure. Unmet needs include partial response and non-response to treatment in many patients, failure to achieve immune homeostasis or drug free remission, and inability to repair damaged tissues. RA is now recognized as the end of a multi-year prodromal phase in which systemic immune dysregulation, likely beginning in mucosal surfaces, is followed by a symptomatic clinical phase. Inflammation and immune reactivity are primarily localized to the synovium leading to pain and articular damage, but is also associated with a broader series of comorbidities. Here, we review recently described immunologic mechanisms that drive breach of tolerance, chronic synovitis, and remission.


Assuntos
Antirreumáticos , Artrite Reumatoide , Sinovite , Humanos , Qualidade de Vida , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Membrana Sinovial
17.
Pediatr Rheumatol Online J ; 20(1): 99, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384772

RESUMO

BACKGROUND: Diagnosing synovial inflammation by administration of gadolinium-based contrast agents is limited by invasiveness and possible side effects, especially in children and adolescents. PURPOSE: We investigated diagnostic accuracy of diffusion-weighted (DWI) MRI with intravoxel incoherent motion (IVIM) imaging compared to contrast-enhanced MRI for detecting synovitis of the knee in a population of pediatrics and young adults. In addition we compared quantitative measures of synovial diffusion and perfusion to a group of healthy volunteers. METHODS: In this prospective study, 8 pediatric patients with 10 symptomatic knees (6 girls and 2 boys, mean age 13 years) with known or suspected synovitis underwent pre- and post-contrast 3.0 T MRI of the knee joint and additional DWI sequences between October 2016 and July 2019. For comparison we enrolled 5 healthy young adults (2 women and 3 men, median age 27 years) with contrast-free MRI of both knees. Post-contrast T1w images and DWI images at b = 1000s/mm2 with apparent diffusion coefficient (ADC) maps of patients were separately rated by two independent and blinded readers with different levels of experience for the presence or absence and degree of synovitis along with the level of confidence. We measured signal intensity on DWI of synovium, joint effusion and muscle with regions of interests and calculated the IVIM-parameters tissue diffusion coefficient (D) and perfusion fraction (f) for patients and volunteers. RESULTS: All patients showed at least some synovial contrast enhancement, 8 (80%) children knees were diagnosed with synovitis on contrast-enhanced (= ce)-T1w, the diagnostic standard. Ratings by the first and second reader on ce-T1w and DWI showed full agreement (kappa = 1) in diagnosing synovitis and substantial agreement (k = 0,655) for the degree of synovial enhancement. Interobserver agreement on DWI showed fair agreement (k = 0,220) between both readers. Diagnostic confidence was lower on DWI. Mean D- and f-values of muscle was comparable between patients and volunteers. Effusion mean D was higher, mean f was lower, synovial mean D was lower, mean f higher in patients than in volunteers. All differences were statistically significant (p < 0.001). CONCLUSIONS: Diffusion-weighted MRI with IVIM imaging remains a promising, though reader-dependent alternative to i.v. contrast-enhanced imaging in pediatric patients to reliably diagnose, or rule out, synovitis of the knee joint. We detected significantly restricted synovial diffusion and increased perfusion in patients compared to healthy volunteers. TRIAL REGISTRATION: Ethical Comitee University Hospital Ulm, Nr. 320/16.


Assuntos
Sinovite , Masculino , Adolescente , Adulto Jovem , Humanos , Criança , Feminino , Adulto , Estudos Prospectivos , Projetos Piloto , Sinovite/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Articulação do Joelho/diagnóstico por imagem
18.
Saudi Med J ; 43(11): 1200-1208, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36379530

RESUMO

OBJECTIVES: To compare the efficacy between platelet-rich plasma (PRP) and corticosteroids (CS) in improving magnetic resonance imaging (MRI)-detected synovitis in correlation with clinical complaints among patients with lumbar facet joint (FJ) disease. METHODS: This study was carried out at Eldemerdash Hospital, Cairo, Egypt between September 2019 and January 2021. A prospective, randomized, comparative, single blinded study included 30 patients with lumbar FJ disease, divided into 2 equal groups, received PRP and CS injections. Patients were comparatively assessed before and after the intervention according to number of tender lumbar FJs, maximum active lumbar extension range of motion, LBP visual analogue score, LBP functional disability questionnaires and MRI lumbar FJ detected synovitis and their grading. RESULTS: Both groups showed a significant improvement in all mentioned parameters at follow-up after 3 months. However, PRP injections promoted better performance in terms of MRI synovitis grade in all lumbar FJ levels compared to CS injections. CONCLUSION: Both PRP and CS injections were effective in improving MRI-detected FJ synovitis while concurrently improving all examined parameters at follow-up after 3 months. However, PRP promoted better improvement in MRI-detected synovitis grade, suggesting that it may be a better treatment option for longer duration efficacy.TRN: NCT04860531- 1/3/2021.


Assuntos
Artropatias , Plasma Rico em Plaquetas , Sinovite , Articulação Zigapofisária , Humanos , Articulação Zigapofisária/patologia , Estudos Prospectivos , Injeções Intra-Articulares , Corticosteroides/uso terapêutico , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Artropatias/tratamento farmacológico , Artropatias/patologia , Resultado do Tratamento
19.
RMD Open ; 8(2)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36410775

RESUMO

OBJECTIVES: Remote assessment of patients with rheumatoid arthritis (RA) has increased during recent years. However, telematic consultations preclude the possibility of carrying out a physical examination and obtaining objective inflammation. In this study, we developed and validated two novel composite disease activity indexes (Thermographic Disease Activity Index (ThermoDAI) and ThermoDAI-CRP) based on thermography of hands and machine learning, in order to assess disease activity easily, rapidly and without formal joint counts. METHODS: ThermoDAI was developed as the sum of Thermographic Joint Inflammation Score (ThermoJIS), a novel joint inflammation score based on the analysis of thermal images of the hands by machine learning, the Patient Global Assessment (PGA) and, for ThermoDAI-CRP, the C reactive protein (CRP). Construct validity was tested in 146 patients with RA by using Spearman's correlation with ultrasound-determined grey-scale synovial hypertrophy (GS) and power Doppler (PD) scores, CDAI, SDAI and DAS28-CRP. RESULTS: Correlations of ultrasound scores with ThermoDAI (GS=0.52; PD=0.56) and ThermoDAI-CRP (GS=0.58; PD=0.61) were moderate to strong, while the correlations of ultrasound scores with PGA (GS=0.35; PD=0.39) and PGA+CRP (GS=0.44; PD=0.46) were weak to moderate. ThermoDAI and ThermoDAI-CRP also showed strong correlations with Clinical Disease Activity Index (ρ>0.83), Simplified Disease Activity Index (ρ>0.85) and Disease Activity Score with 28-Joint Counts-CRP (ρ>0.81) and high sensitivity for detecting active synovitis using remission criteria. CONCLUSIONS: ThermoDAI and ThermoDAI-CRP showed stronger correlations with ultrasound-determined synovitis than PGA and PGA + CRP, thus presenting an opportunity to improve remote consultations with patients with RA.


Assuntos
Artrite Reumatoide , Sinovite , Humanos , Termografia , Prostaglandinas A , Artrite Reumatoide/diagnóstico , Proteína C-Reativa , Inflamação
20.
Front Immunol ; 13: 973243, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325356

RESUMO

Spondyloarthritis (SpA) comprises a number of inflammatory rheumatic diseases with overlapping clinical manifestations. Strong association with several HLA-I alleles and T cell infiltration into an inflamed joint suggest involvement of T cells in SpA pathogenesis. In this study, we performed high-throughput T cell repertoire profiling of synovial fluid (SF) and peripheral blood (PB) samples collected from a large cohort of SpA patients. We showed that synovial fluid is enriched with expanded T cell clones that are shared between patients with similar HLA genotypes and persist during recurrent synovitis. Using an algorithm for identification of TCRs involved in immune response we discovered several antigen-driven CD8+ clonal groups associated with risk HLA-B*27 or HLA-B*38 alleles. We further show that these clonal groups were enriched in SF and had higher frequency in PB of SpA patients vs healthy donors, implying their relevance to SpA pathogenesis. Several of the groups were shared among patients with different SpAs that suggests a common immunopathological mechanism of the diseases. In summary, our results provide evidence for the role of specific CD8+ T cell clones in pathogenesis of SpA.


Assuntos
Espondilartrite , Sinovite , Humanos , Líquido Sinovial , Receptores de Antígenos de Linfócitos T , Linfócitos T CD8-Positivos , Espondilartrite/genética
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