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OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.
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Entesopatia , Espondilartrite , Ultrassonografia Doppler , Humanos , Feminino , Masculino , Entesopatia/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Ultrassonografia Doppler/métodos , Espondilartrite/diagnóstico por imagem , Espondilartrite/complicações , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/complicações , Índice de Gravidade de Doença , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/patologia , Estudos de Casos e ControlesRESUMO
OBJECTIVES: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. METHODS: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. RESULTS: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. CONCLUSIONS: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.
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Entesopatia , Humanos , Reprodutibilidade dos Testes , Entesopatia/diagnóstico por imagem , Ultrassonografia/métodos , Ultrassonografia Doppler/métodos , InternetRESUMO
OBJECTIVES: To identify the subpopulation of rheumatoid arthritis (RA) non-responders to Janus kinase inhibitors (JAKis) using cluster analysis. METHODS: This retrospective study enrolled RA patients who had been treated with JAKis (tofacitinib or baricitinib) between July 2013 and September 2019 in six centres. The endpoint was set as inadequate response to JAKis (JAKis-IR), defined as either non-response to JAKis or their intolerance. Non-response to JAKis was defined as achieving neither American College of Rheumatology 20% response nor Disease Activity Score (ΔDAS28-CRP) >1.2 at 12 weeks. Withdrawal time point included earlier than after 12 weeks from baseline. A hierarchical cluster analysis was performed with variables related with clinical and serological parameters at baseline. RESULTS: The 132 RA patients enrolled were classified into four groups (Group A-D). Groups consisted of three components defined at baseline, as seropositivity, advanced joint destruction, interstitial lung disease presumably associated with RA (RA-ILD). Group A (n=32): seronegative, presence of advanced joint destruction, absence of RA-ILD. Group B (n=35): seropositive, absence of advanced joint destruction and RA-ILD. Group C (n=20): seropositive, absence of advanced joint destruction, presence of RA-ILD. Group D (n=45): seropositive, presence of advanced joint destruction and RA-ILD. The rate of JAKis-IR in four groups was as follows: A, 34.3%; B, 17.1%; C, 20.0%; and D, 8.9%. The difference in JAKis-IR rate between group A and D was statistically significant. CONCLUSIONS: A subpopulation of RA patients with a combination of the following three components, seronegativity, advanced joint destruction and absence of RA-ILD, was identified as being prone to JAKis-IR.
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Artrite Reumatoide , Inibidores de Janus Quinases , Doenças Pulmonares Intersticiais , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Análise por Conglomerados , Humanos , Inibidores de Janus Quinases/efeitos adversos , Doenças Pulmonares Intersticiais/complicações , Estudos RetrospectivosRESUMO
OBJECTIVES: We aimed to evaluate whether gadolinium-enhanced magnetic resonance imaging (MRI) in shoulders can contribute to more accurate diagnosis and prediction of recurrence in patients with polymyalgia rheumatica (PMR). METHODS: Gadolinium-enhanced MRI and ultrasonography (US) in shoulders were performed in the patients who had bilateral shoulders pain and fulfilled the Bird's Classification Criteria between June 2012 and June 2018. PMR was clinically diagnosed by at least two rheumatologists. MRI and US findings assessed by independent radiologists were compared between the PMR or non-PMR patients. PMR patients were treated with 20 mg/day of prednisolone and were followed-up until June 2019 to determine any recurrences of the disease. RESULTS: PMR was diagnosed in 58 of 137 patients received gadolinium-enhanced MRI and US examinations. Enhancement of joint capsule, enhancement of rotator cuff tendon and focal bone oedema in humerus heads were frequently found in the PMR patients. If the three findings were used in combination to diagnose PMR, MRI had 76% sensitivity and 85% specificity, higher compared to US findings, which had 50% sensitivity and 72% specificity. During follow-up, PMR recurred in 24 patients. Patients with recurrent PMR were younger in age, had less enhancement of rotator cuff tendon and more synovial hypertrophy findings on their MRI. CONCLUSIONS: Gadolinium-enhanced MRI could display capsulitis, rotator cuff tendonitis and focal bone oedema in humerus heads that was sensitive and specific to patients with PMR, improving diagnostic accuracy in PMR. Rotator cuff tendonitis and synovial hypertrophy on MRI could help predict recurrence in PMR.
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Gadolínio , Polimialgia Reumática , Humanos , Imageamento por Ressonância Magnética , Polimialgia Reumática/diagnóstico por imagem , Polimialgia Reumática/tratamento farmacológico , Recidiva , OmbroRESUMO
The pleiotropic effects of statins, including an antiarthritic potential, have been noted. This study aimed to determine the efficacy of statins on rheumatoid arthritis (RA) and clarify how statins affect its pathogenesis. Fluvastatin (500 µg/kg/day) or vehicle was given per os to env-pX rats, which carry the human T-cell leukemia virus type I env-pX gene and spontaneously develop destructive arthritis mimicking RA, for 30 days. Blood sampling and ultrasonography (US) of the ankle joints were conducted on days 0, 10, 20, and 30. On day 30, all rats were euthanized, and the ankle joints were subjected to histological analysis. To clarify how fluvastatin affects the pathogenesis of RA, comprehensive serum exosomal microRNA (miRNA) analysis was performed. Gene expression in the primary culture of synovial fibroblasts derived from arthritic rat and human and non-arthritic rat periarticular tissues was determined quantitatively by real-time reverse transcription-polymerase chain reaction (RT-PCR). As a result, the development of arthritis in env-pX rats was significantly suppressed by fluvastatin, which was evident from the viewpoints of serology, US imaging, and histology. Comprehensive serum exosomal miRNA analysis suggested that the expression of Rho GTPase-activating protein 12 (Arhgap12) was decreased in arthritic env-pX rats but increased with the administration of fluvastatin. Corresponding results were obtained by quantitative RT- PCR using primary culture of synovial fibroblasts. The collective findings suggest that fluvastatin prevents the development of arthritis in env-pX rats via the up-regulation of ARHGAP12. This study suggests that ARHGAP12 can be a possible therapeutic target of RA.
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Artrite Experimental/tratamento farmacológico , Artrite Experimental/prevenção & controle , Fluvastatina/uso terapêutico , Proteínas Ativadoras de GTPase/metabolismo , Regulação para Cima , Animais , Artrite Experimental/diagnóstico por imagem , Artrite Experimental/patologia , Exossomos/efeitos dos fármacos , Exossomos/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fluvastatina/farmacologia , Proteínas Ativadoras de GTPase/genética , Humanos , Inflamação/patologia , Articulações/diagnóstico por imagem , Articulações/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Membrana Sinovial/patologia , Regulação para Cima/efeitos dos fármacosRESUMO
NKT cells are defined as T cells that recognize hydrophobic antigens presented by class I MHC-like molecules, including CD1d. Among CD1d-restricted NKT cells, type I and type II subsets have been noted. CD1d-restricted type I NKT cells are regarded as pro-inflammatory cells in general. On the contrary, accumulated evidence has demonstrated an anti-inflammatory property of CD1d-restricted type II NKT cells. In our earlier study using a rat model with vasculitis, we demonstrated the pro-inflammatory function of CD1d-restricted type II NKT cells and identified that one such cell recognized P518-532 of rat sterol carrier protein 2 (rSCP2518-532 ), which appeared on vascular endothelial cells presented by CD1d. Based on this evidence, we attempted to detect human CD1d-restricted type II NKT cells in peripheral blood using hSCP2518-532 , the human counterpart of rSCP2518-532, together with a CD1d tetramer in flow cytometry. First, we determined the binding of hSCP2518-532 to CD1d. Next, we detected CD3-positive hSCP2518-532 -loaded CD1d (hSCP2518-532 /CD1d) tetramer-binding cells in peripheral blood of healthy donors. The abundance of TGF-ß-producing cells rather than TNF-α-producing cells in CD3-positive hSCP2518-532 /CD1d tetramer-binding cells suggests the anti-inflammatory property of SCP2-loaded CD1d (SCP2/CD1d) tetramer-binding type II NKT cells in healthy individuals. Furthermore, we compared cytokine profile between healthy individuals and patients with vasculitis in a pilot study. Interestingly, the percentage of TGF-ß-producing cells in SCP2/CD1d tetramer-binding type II NKT cells in vasculitic patients was significantly lower than that in healthy controls despite the greater number of these cells. Although further studies to clarify the mechanism and significance of this phenomenon are needed, SCP2/CD1d tetramer-binding type II NKT cells in peripheral blood should be examined in more detail to understand the pathophysiology of vasculitides in humans. © 2018 International Society for Advancement of Cytometry.
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Células T Matadoras Naturais/imunologia , Vasculite/imunologia , Adulto , Idoso , Antígenos CD1d/imunologia , Complexo CD3/imunologia , Proteínas de Transporte/imunologia , Feminino , Voluntários Saudáveis , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fator de Crescimento Transformador beta/imunologia , Adulto JovemRESUMO
OBJECTIVES: Presepsin (PSEP: soluble CD14 subtype) is produced from bacteria-stimulated monocytes or neutrophils, thus recognized as a biomarker of sepsis. Aberrant functions in monocyte or neutrophils are increasingly recognized in systemic lupus erythematosus (SLE). We investigated whether plasma PSEP reflects disease activity in patients with SLE. METHODS: This retrospective study comprised 35 patients with SLE and 72 with non-SLE autoimmune diseases who visited our facility during the period from August 2012 to September 2015. Plasma PSEP levels and laboratory data were compared between SLE and non-SLE. Clinical markers of SLE disease activity, including SLE disease activity index 2000 (SLEDAI-2K), serum complement concentrations and serum anti-ds-DNA antibodies were assessed in correlation with plasma PSEP levels. RESULTS: Plasma PSEP levels in SLE were higher than those in non-SLE. This phenomenon holds true when comparing SLE and non-SLE patients in the absence of infection (p = .0008). Plasma PSEP levels in SLE patients negatively correlated with C3 (r = -0.4454, p = .0430), CH50 (r = -0.4502, p = .0406) and positively with SLEDAI-2K (r = 0.4801, p = .0237). CONCLUSION: Elevated plasma PSEP levels were correlated with disease activity of SLE, suggesting inappropriate monocyte or neutrophil activation in the pathophysiology of SLE exacerbation.
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Receptores de Lipopolissacarídeos/sangue , Lúpus Eritematoso Sistêmico/sangue , Fragmentos de Peptídeos/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Structural variation in the stroma-grana (SG) arrangement of the thylakoid membranes, such as changes in the thickness of the grana stacks and in the ratio between grana and inter-grana thylakoid, is often observed. Broadly, such alterations are considered acclimation to changes in growth and the environment. However, the relation of thylakoid morphology to plant growth and photosynthesis remains obscure. Here, we report changes in the thylakoid during leaf development under a fixed light condition. Histological studies on the chloroplasts of fresh green Arabidopsis leaves have shown that characteristically shaped thylakoid membranes lacking the inter-grana region, referred to hereafter as isolated-grana (IG), occurred adjacent to highly ordered, large grana layers. This morphology was restored to conventional SG thylakoid membranes with the removal of bolting stems from reproductive plants. Statistical analysis showed a negative correlation between the incidences of IG-type chloroplasts in mesophyll cells and the rates of leaf growth. Fluorescence parameters calculated from pulse-amplitude modulated fluorometry measurements and CO2 assimilation data showed that the IG thylakoids had a photosynthetic ability that was equivalent to that of the SG thylakoids under moderate light. However, clear differences were observed in the chlorophyll a/b ratio. The IG thylakoids were apparently an acclimated phenotype to the internal condition of source leaves. The idea is supported by the fact that the life span of the IG thylakoids increased significantly in the later developing leaves. In conclusion, the heterogeneous state of thylakoid membranes is likely important in maintaining photosynthesis during the reproductive phase of growth.
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Fotossíntese/fisiologia , Reprodução/fisiologia , Tilacoides/metabolismo , Folhas de Planta/metabolismoRESUMO
γ-Secretase is an intramembrane-cleaving protease responsible for the generation of amyloid-ß (Aß) peptides. Recently, a series of compounds called γ-secretase modulators (GSMs) has been shown to decrease the levels of long toxic Aß species (i.e., Aß42), with a concomitant elevation of the production of shorter Aß species. In this study, we show that a phenylimidazole-type GSM allosterically induces conformational changes in the catalytic site of γ-secretase to augment the proteolytic activity. Analyses using the photoaffinity labeling technique and systematic mutational studies revealed that the phenylimidazole-type GSM targets a previously unidentified extracellular binding pocket within the N-terminal fragment of presenilin (PS). Collectively, we provide a model for the mechanism of action of the phenylimidazole-type GSM in which binding at the luminal side of PS induces a conformational change in the catalytic center of γ-secretase to modulate Aß production.
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Secretases da Proteína Precursora do Amiloide/metabolismo , Imidazóis/farmacologia , Regulação Alostérica/efeitos dos fármacos , Aminoácidos/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Domínio Catalítico , Ativação Enzimática/efeitos dos fármacos , Fluorescência , Humanos , Imidazóis/química , Modelos Moleculares , Mutação/genética , Peptídeos/metabolismo , Homologia Estrutural de Proteína , Especificidade por Substrato/efeitos dos fármacosAssuntos
Colite Ulcerativa/etiologia , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Arterite de Takayasu/complicações , Arterite de Takayasu/tratamento farmacológico , Adulto , Feminino , Humanos , Indução de Remissão/métodosAssuntos
Cardiopatias/complicações , Hipertensão Pulmonar/etiologia , Doenças Musculares/etiologia , Feminino , Cardiopatias/diagnóstico por imagem , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Doenças Musculares/diagnóstico por imagem , Radiografia TorácicaRESUMO
Recent progress in treatment and imaging enables us to aim the clinical remission in rheumatoid arthritis. In terms of achieving deep remission (structural remission) and predicting prognosis, useful serological biomarkers are now expected. Recently, some of the serological biomarkers, such as RANKL (receptor activator of NF-κB ligand) and TRACP (tartrate-resistant acid phopshatate)-5b, are used to assess the activity of rheumatoid arthritis. The levels of these biomarkers well reflect bone erosion but are less affected by age or physiological variation.
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Artrite Reumatoide/imunologia , Doenças Ósseas/imunologia , Doenças das Cartilagens/imunologia , Osteoclastos/imunologia , Biomarcadores/análise , Colágeno/análise , Humanos , Osteoclastos/químicaRESUMO
OBJECTIVES: i) To explore the agreement between the OMERACT ultrasound lesions of enthesitis and physical examination in assessing enthesitis in spondyloarthritis (SpA) patients; ii) To investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centres participated in this cross-sectional study. SpA patients, including axial SpA (axSpA) and psoriatic arthritis (PsA) patients, underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for 'active enthesitis' by our group. Subclinical enthesitis was defined as the presence of 'active enthesitis' in ≥1 enthesis in SpA patients without clinical enthesitis (i.e., number of positive entheses on physical examination and Leeds Enthesitis Index score =0). RESULTS: 4130 entheses in 413 SpA patients (224 axSpA/189 PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (i.e., enthesophytes) to almost perfect (i.e., power Doppler and 'active enthesitis'). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158/413 (38.3%) SpA patients with clinical enthesitis, 108 (68.4%) exhibited no 'active enthesitis' on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of SpA patients with and without subclinical enthesitis. CONCLUSIONS: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in SpA patients.
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Objectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases. Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0-3) and a continuous quantitative measurement ("VAS echogenicity," 0-100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall's Tau and Pearson's Rho coefficients. Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57-0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68-0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. "VAS echogenicity" showed a high reliability both in the inter-observer [ICC = 0.80 (0.75-0.85)] and intra-observer [ICC = 0.88 (0.88-0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and "VAS echogenicity" [ICC = 0.52 (0.50-0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively). Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases.
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Ultrasound (US) is a promising tool for assessing sarcopenia. We aimed to test in the rheumatology setting two US scanning protocols to measure muscle thickness (MT) at the anterior thigh level and to assess their feasibility and reliability. In the first phase of the study, three rheumatologists performed a US examination on 19 consecutive patients adopting two scanning protocols, namely the anterior superior iliac spine (ASIS) and the greater trochanter techniques. After consensus was obtained on the easiest scanning protocol to perform, two rheumatologists adopted only the ASIS technique in 40 consecutive patients. MT measurements were recorded as well as the time needed to complete each scanning protocol bilaterally. The median time needed to complete the US examination was under 5 minutes for each of the two techniques, with no significant difference between them (p = 0.64). In the first phase, we found an excellent inter-observer reliability of the proposed scanning protocols, with a higher but nonstatistically significant intraclass correlation coefficient (ICC) for the ASIS technique compared with the greater trochanter technique (ICC 0.97 vs. ICC 0.92, p = 0.05). The ASIS technique had a significantly higher intra-observer reliability (ICC 0.97 vs. ICC 0.92, p < 0.01). In the second phase, the ASIS technique confirmed on a larger sample its excellent inter-observer reliability, with an ICC of 0.96. The present study presents a novel tool for assessing sarcopenia and provides evidence in favor of feasibility and reliability of US measurement of MT at the anterior thigh level in rheumatology setting. Key Points ⢠This study demonstrates that ultrasound (US) measurement of muscle thickness at the anterior thigh level is highly reliable, especially for the "anterior superior iliac spine (ASIS)" technique. ⢠The short time needed to complete the US assessment highlights the feasibility of the proposed scanning protocols. ⢠The simplicity and conciseness of the proposed techniques will allow other researchers and clinicians to use it for a fast assessment of sarcopenia.
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Reumatologia , Coxa da Perna , Humanos , Músculos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Coxa da Perna/diagnóstico por imagem , UltrassonografiaRESUMO
This study aimed to determine whether ultrasonography (US) can detect increased vascular signal in the synovial tissue before overt synovitis in rheumatoid arthritis (RA). Env-pX rats that spontaneously develop RA-like synovitis were used. Ankle joints of 15 pre-morbid env-pX rats were observed with power Doppler and superb microvascular imaging (SMI) using an ultrahigh-frequency (8-24 MHz) probe. Signal values were counted as the number of pixels. The total number of vessels and vessel area in the synovial tissue were histologically evaluated. Dilated vessels were determined from the mean value of synovial vessels in three wild-type rats. In all env-pX rats, apparent synovial proliferation was not observed. However, vasodilation was evident. Only SMI values were significantly correlated with the number of dilated vessels (râ¯=â¯0.585, pâ¯=â¯0.022) but not with the total number of vessels. US with SMI using ultrahigh-frequency probe can detect increased vascular signal in the synovial tissue of arthritis-prone rats.
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Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/patologia , Ultrassonografia/métodos , Animais , Articulação do Tornozelo/irrigação sanguínea , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/patologia , Modelos Animais de Doenças , Ratos , Índice de Gravidade de Doença , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologiaRESUMO
Pulmonary hypertension associated with large vessel pulmonary arteritis (LVPA) has been reported in the course of Takayasu arteritis (TAK). Biologic therapies targeting inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin-6, have recently been successful to treat refractory TAK. Infliximab (IFX), an anti-TNF-α antibody and tocilizumab (TCZ), an anti-IL-6 receptor antibody may have similar efficacy and safety profile in the treatment of TAK. However, some cases are refractory to TNF inhibitors but respond to TCZ, and vice versa. Here, we report a severe case of LVPA, who was successfully treated with IFX but was refractory to TCZ and presented a discrepancy between serum C-reactive protein levels and fluorodeoxyglucose vascular positivity. This case would indicate heterogeneity of pathogenic mechanisms in LVPA and TAK.