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Rheumatoid arthritis (RA) is an inflammatory joint disease characterized by persistent synovitis and inflammation. The exact mechanism of mitochondrial function in the presence of inflammation and dysregulation of autophagic processes in the pathogenesis of RA is still unclear. The aim of our study is to determine mitochondrial function, gene and protein levels of biomolecules related to inflammation (YKL-40) and autophagy (LAMPs) and to search a connection between them in the RA context. Twenty newly diagnosed RA patients and ten healthy individuals were included in the study. Disease severity was assessed by ultrasonography. Conventional clinico-laboratory parameters, immunological markers and protein levels of LAMPs and YKL-40 were examined in plasma. Gene expression analysis for the quantitative measurement of LAMPs and YKL-40 were conducted in white blood cells (WBC). A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in peripheral blood mononuclear cells (PBMCs). Increase in spare respiratory capacity in PBMCs of RA patients was detected. Decreased LAMPs plasma protein levels and increased protein levels of YKL-40 in RA patients compared to healthy individuals were measured. No significant differences were found in gene expressions. Correlations between mitochondrial, ultrasonographic and protein levels of the biomarkers related with inflammation and autophagy were established. New data on mitochondrial dysfunction in RA patients and links to inflammation and mitophagy are reported. The relationship between dysregulation of mitophagy and joint diseases deserves to be thoroughly investigated as it would be a promising therapeutic approach.
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Chemerin and resistin are adipokines studied as potential markers for early diagnosis and disease severity in patients with knee osteoarthritis (KOA) Therefore, we aimed to investigate the associations serum and synovial levels of chemerin and resistin with inflammatory parameters and ultrasonographic scores (US) in KOA individuals. Serum was collected from 28 patients with KOA and synovial fluid was obtained from 16 of them. Another 31 age and sex matched cases with no joint disease were included as healthy controls. Concentrations of chemerin, resistin, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were determined with ELISA. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum uric acid (UA) were measured in the patients group. Participants with KOA underwent US assessment using the Outcome Measures in Rheumatology (OMERACT) scores. Patients with KOA had statistically significant higher level of serum resistin than healthy controls [11.05 (3.78-24.13) ng/mL and 7.23 (3.83-12.19) respectively, p < 0.001]. A strong correlation was found between serum chemerin and ESR (r = 0.434, p = 0.021), uric acid (r = 0.573, p = 0.001) as well as the US (r=-0.872, p < 0.001). Serum resistin demonstrated significant association with TNF-alpha (r = 0.398, p = 0.044). In conclusion, both chemerin and resistin might contribute to inflammatory changes associated with KOA. Further studies are needed to elucidate their potential role in the pathogenesis of the disease.
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ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Artrite Reumatoide , Aterosclerose , Biomarcadores , Espessura Intima-Media Carotídea , Interleucina-6 , Humanos , Interleucina-6/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico por imagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Biomarcadores/sangue , Prognóstico , Adulto , Aterosclerose/sangue , Aterosclerose/diagnóstico por imagem , Aterosclerose/etiologia , Aterosclerose/diagnóstico , Idoso , Estudos de Casos e Controles , Artérias Carótidas/diagnóstico por imagem , Valor Preditivo dos Testes , Ultrassonografia das Artérias CarótidasRESUMO
Systemic sclerosis is a complex idiopathic disease originating from an intricate interplay between genetic susceptibility, environmental factors, and epigenetic modifications. This scoping review aims to map the advancements made regarding DNA methylation abnormalities and histone modifications in systemic sclerosis in the past decade. A literature search was conducted using three electronic databases (Scopus, Web of Science and PubMed) to identify relevant articles. A total of 44 studies were selected for this review, demonstrating the critical contribution of epigenetic perturbations in multiple cell types to disease pathogenesis. In conclusion, this scoping review has elucidated the significant discoveries made in the past decade regarding the role of DNA methylation and histone modifications in systemic sclerosis. Further progress in the field could lead to the development of novel treatment possibilities targeting epigenetic marks.
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OBJECTIVES: Over the last years ultrasound has shown to be an important tool for evaluating lung involvement, including interstitial lung disease (ILD) a potentially severe systemic involvement in many rheumatic and musculoskeletal diseases (RMD). Despite the potential sensitivity of the technique the actual use is hampered by the lack of consensual definitions of elementary lesions to be assessed and of the scanning protocol to apply. Within the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group we aimed at developing consensus-based definitions for ultrasound detected ILD findings in RMDs and assessing their reliability in dynamic images. METHODS: Based on the results from a systematic literature review, several findings were identified for defining the presence of ILD by ultrasound (i.e., Am-lines, B-lines, pleural cysts and pleural line irregularity). Therefore, a Delphi survey was conducted among 23 experts in sonography to agree on which findings should be included and on their definitions. Subsequently, a web-reliability exercise was performed to test the reliability of the agreed definitions on video-clips, by using kappa statistics. RESULTS: After three rounds of Delphi an agreement >75 % was obtained to include and define B-lines and pleural line irregularity as elementary lesions to assess. The reliability in the web-based exercise, consisting of 80 video-clips (30 for pleural line irregularity, 50 for B-lines), showed moderate inter-reader reliability for both B-lines (kappa = 0.51) and pleural line irregularity (kappa = 0.58), while intra-reader reliability was good for both B-lines (kappa = 0.72) and pleural line irregularity (kappa = 0.75). CONCLUSION: Consensus-based ultrasound definitions for B-lines and pleural line irregularity were obtained, with moderate to good reliability to detect these lesions using video-clips. The next step will be testing the reliability in patients with ILD linked to RMDs and to propose a consensual and standardized protocol to scan such patients.
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Técnica Delphi , Doenças Pulmonares Intersticiais , Ultrassonografia , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Ultrassonografia/normas , Reprodutibilidade dos Testes , Pulmão/diagnóstico por imagem , ConsensoRESUMO
OBJECTIVE: The main objective of this study was to analyse the prevalence and characteristics of subclinical GCA in patients with PMR. METHODS: This was a cross-sectional multicentre international study of consecutive patients with newly diagnosed PMR without symptoms or signs suggestive of GCA. All patients underwent US of the temporal superficial, common carotid, subclavian and axillary arteries. Patients with halo signs in at least one examined artery were considered to have subclinical GCA. The clinical, demographic and laboratory characteristics of the PMR group without subclinical vasculitis were compared with subclinical GCA, and the pattern of vessel involvement was compared with that of a classical single-centre GCA cohort. RESULTS: We included 346 PMR patients, 267 (77.2%) without subclinical GCA and 79 (22.8%) with subclinical GCA. The PMR patients with subclinical GCA were significantly older, had a longer duration of morning stiffness and more frequently reported hip pain than PMR without subclinical GCA. PMR with subclinical GCA showed a predominant extracranial large vessel pattern of vasculitic involvement compared with classical GCA, where the cranial phenotype predominated. The patients with PMR in the classical GCA group showed a pattern of vessel involvement similar to classical GCA without PMR but different from PMR with subclinical involvement. CONCLUSION: More than a fifth of the pure PMR patients had US findings consistent with subclinical GCA. This specific subset of patients showed a predilection for extracranial artery involvement. The optimal screening strategy to assess the presence of vasculitis in PMR remains to be determined.
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Arterite de Células Gigantes , Polimialgia Reumática , Humanos , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/diagnóstico , Polimialgia Reumática/epidemiologia , Polimialgia Reumática/diagnóstico , Prevalência , Estudos Transversais , DorRESUMO
The COVID-19 hurt various lifestyle aspects, especially the treatment and follow-up of patients with chronic diseases such as autoimmune inflammatory rheumatic diseases (RD). The new circumstances changed the frequency of medical examinations and the way patients with rheumatic diseases are followed up. The objective is to study the impact of COVID-19 on RD patients' satisfaction with access to medical services. A national multicenter observational cross-sectional anonymous online survey was conducted on patients with RD using a specially developed web-based platform and structured questionnaire https://rheumatologycovid19.bg/ . The study was carried out with the support of intra-university project â6/2022 MU-Plovdiv. 1288 patients participated, with an average age of 47.03 (SD ± 12.80 years), of whom 992 (81.6%) were women. The questionnaire contained 41 questions grouped into 5 panels. Descriptive statistics were used-mean, alternative analysis, logistic regression and Decision Tree using the CRT (classification and regression trees) method. The study found that RD patients' satisfaction with access to medical services was influenced by communication type and the frequency of visits to the rheumatologist, difficulties in prescribing and finding medicines and the presence of comorbidities. The likelihood of patients' satisfaction with their rheumatologist was 5.5 and 3 times higher for in-person and other means of communication, respectively, compared to those without any communication. The relative share of patients who communicated by phone was larger (59%) compared to pre-pandemic (41%), where direct contact with the physician prevailed (80%). The results of the study confirmed the need to optimize remote access to medical care for patients with RD during the pandemic.
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COVID-19 , Doenças Reumáticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Satisfação do Paciente , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/terapia , AdultoRESUMO
OBJECTIVE: The aim of the present study was to determine the clinical significance of subclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) and ascertain its optimal treatment approach. METHODS: Patients with PMR who fulfilled the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology Provisional Classification Criteria for PMR, did not have GCA symptoms and were routinely followed up for 2 years and were stratified into two groups, according to their ultrasound results: isolated PMR and PMR with subclinical GCA. The outcomes (relapses, glucocorticoid use and disease-modifying antirheumatic drug treatments) between groups were compared. RESULTS: We included 150 patients with PMR (50 with subclinical GCA) with a median (IQR) follow-up of 22 (20-24) months. Overall, 47 patients (31.3 %) had a relapse, 31 (62%) in the subclinical GCA group and 16 (16%) in the isolated PMR group (p<0.001). Among patients with subclinical GCA, no differences were found in the mean (SD) prednisone starting dosage between relapsed and non-relapsed patients (32.4±15.6 vs 35.5±12.1 mg, respectively, p=0.722). Patients with subclinical GCA who relapsed had a faster prednisone dose tapering in the first 3 months compared with the non-relapsed patients, with a mean dose at the third month of 10.0±5.2 versus 15.2±7.9 mg daily (p<0.001). No differences were found between relapsing and non-relapsed patients with subclinical GCA regarding age, sex, C reactive protein and erythrocyte sedimentation rate. CONCLUSIONS: Patients with PMR and subclinical GCA had a significantly higher number of relapses during a 2-year follow-up than patients with isolated PMR. Lower starting doses and rapid glucocorticoid tapering in the first 3 months emerged as risk factors for relapse.
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Arterite de Células Gigantes , Polimialgia Reumática , Humanos , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/complicações , Polimialgia Reumática/complicações , Prednisona/uso terapêutico , Glucocorticoides/uso terapêutico , RecidivaRESUMO
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated by inflammation of the synovial tissue and autoantibody production. Oxidative stress and free radicals are known to be indirectly implicated in joint damage and cartilage destruction in RA. Several studies describe the presence of mitochondrial dysfunction in RA, but few of them follow the dynamics in energy parameters after therapy. The aim of our investigation is to evaluate the direct effect of JAK inhibitors on cellular metabolism (and under induced oxidative stress) in RA patients. Ten newly diagnosed RA patients were included in the study. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated before and 6 months after therapy with JAK inhibitors. A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in PBMCs. Sonographic examination, DAS28 and conventional clinical laboratory parameters were determined also prior and post therapy. A significant decrease in proton leak after therapy with JAK inhibitors was found. The increased production of ATP indicates improvement of cellular bioenergetics status. These findings could be related to the catalytic action of JAK inhibitors on oxidative phosphorylation which corresponds to the amelioration of clinical and ultra-sonographic parameters after treatment. Our study is the first to establish the dynamics of mitochondrial parameters in PBMCs from RA patients before and after in vivo therapy with JAK inhibitors.
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Artrite Reumatoide , Inibidores de Janus Quinases , Humanos , Inibidores de Janus Quinases/uso terapêutico , Projetos Piloto , Leucócitos Mononucleares/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Mitocôndrias/metabolismo , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/uso terapêuticoRESUMO
Eosinophilic fasciitis (EF) remains a rare condition without precise diagnostic criteria due to common symptoms with other autoimmune diseases requiring broad differential diagnosis. This paper describes the use of high-resolution musculoskeletal ultrasonography and elastography in the diagnosis and follow-up of eosinophilic fasciitis through the case of a 56-year-old male patient. In addition to laboratory data, instrumental data, and biopsy, musculoskeletal ultrasonography (US) was used both in the diagnostic process and in the follow-up period for an objective assessment of the changes in the patient's condition and response to treatment. The US showed disorganization of the myofibrils adjacent to the superficial fascia, edema, and thickening of the fascia and subcutaneous edema. In addition, the use of shear-wave elastography (SWE) demonstrated significantly reduced skin elasticity. High-frequency musculoskeletal ultrasound in combination with SWE is an effective method both for the diagnosis of EF and for the follow-up of the changes occurring after therapy. Based on the fact that it can easily differentiate the substrate of involvement, such as skin, subcutaneous tissue, or muscle fascia, ultrasound can be used to distinguish EF from other skin and muscle diseases.
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Rheumatoid arthritis is an inflammatory joint disease that causes progressive joint damage, leading to severe disability. Early diagnosis, optimal therapy, and strict adherence to the prescribed medication are key factors that allow for the cessation of the disease progression and the preserving of the patient's quality of life. The objective of this study was to estimate the compliance to and persistence of biologic disease-modifying anti-rheumatic drugs (bDMARDs) among the Bulgarian population with RA. This retrospective observational cohort study included 179 patients, who were tracked over a 36-month period. During baseline and subsequent follow-up visits (at months 6, 12, 24, and 36), we monitored the disease activity, side effects, medication tolerability and effectiveness, compliance, and persistence to the prescribed biologic agent. The compliance with bDMARDs among Bulgarian patients with RA was 85.5% in the first year, 76.0% in the second year, and 63.7% in the third year. The Infliximab cohort showed the lowest compliance rate (50%), with the other subgroups bDMARDs having similar results (64-70%) during the period of observation. The median therapy duration across all patient cohorts is 61.9 months (IQR 55.7-67.6). Our study did not establish any significant impact of gender, age and disease duration, concomitant treatment with methotrexate, type of biologic agent and previous exposure to biological agents on the treatment adherence. The compliance with and persistence of the prescribed bDMARD among the Bulgarian population with RA is unsatisfactory. Therapy interruption and nonadherence to recommended therapy are associated with disease progression and patient disability. The consequences include not only financial burdens but also psychosocial and physical impacts.
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The advent of biologic disease-modifying antirheumatic drugs has dramatically changed the comprehensions of treatment and long-term prognosis in patients with rheumatoid arthritis. The potent therapeutic results can only be achieved if the patients adhere to prescribed medications. The objective of this study was to estimate the impact of age, gender, duration of the disease, concomitant Methotrexate therapy, prior exposure to biologic agents, disease activity, functional capacity, and health-related quality of life on adherence to biologic treatment among Bulgarian population with rheumatoid arthritis. This was a retrospective observational cohort study that included 179 patients. At the baseline visit and subsequent follow-up assessments at 6, 12, 24 and 36 months, patients were interviewed by a physician and underwent physical examinations. We monitored the changes in disease activity, functional capacity and health-related quality of life on each time point. Univariate and multivariate binary logistic regression was used to determine the prognostic value of possible predictors of treatment adherence. Our findings showed that only DAS28 score [odd ratio (OR) = 1.174; 95% CI 1.74-2.362] and HAQ score (OR 2.803; 95% CI 1.428-5.503) remained significant for the treatment adherence throughout the study period. The adherence to the biologic disease-modifying anti-rheumatic drugs among Bulgarian patients with rheumatoid arthritis is suboptimal. A multifaceted and comprehensive knowledge of the influencing factors can be useful for the development of different strategies that can improve treatment adherence.
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Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Humanos , Estudos de Coortes , Estudos Retrospectivos , Qualidade de Vida , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Terapia Biológica , Produtos Biológicos/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: Rheumatoid arthritis (RA) is the most common inflammatory joint disease. Various proinflammatory cytokines are involved in the pathogenesis of this chronic disorder. It is characterized by the presence of autoantibodies, such as rheumatoid factor and antibodies against citrullinated peptides. The present study focuses on investigation of possible association between the proinflammatory cytokine interleukin 17 and anti-CCP, anti-MCV, and anti-CarP antibodies seropositivity in RA patients. AIM: To assess serum levels of interleukin 17 (IL-17) in patients with rheumatoid arthritis and healthy controls (HC) and to investigate the relationship between IL-17 and anti-cyclic citrullinated protein (anti-CCP) antibodies, antimutated citrullinated vimentin (anti-MCV) antibodies, and anti-carbamylated protein (anti-CarP) antibodies in patients with RA. MATERIALS AND METHODS: Forty-seven patients diagnosed with rheumatoid arthritis and 44 healthy controls were included in the study. Serum IL-17 levels were examined in all participants. Anti-CCP, anti-MCV, and anti-CarP antibodies were tested in the group of RA patients. RESULTS: The mean serum level of IL-17 in RA patients was higher (12.8 pg/ml) than that in healthy controls (7.9 pg/ml), but the difference was not statistically significant (p=0.276). No significant correlation was observed between anti-CCP (+/-) and IL-17 (rs=0.162, p=0.380), and between anti-MCV (+/-) and IL-17 (rs=0.157, p=0.340). A significant positive correlation of moderate value was reported between anti-CarP (+/-) and IL-17 (rs=0.388, p=0.015). CONCLUSIONS: The present study demonstrated that the IL-17 serum levels in RA patients were increased compared to healthy controls. No correlation was found between ACPA immunological markers and IL-17 levels in patients with RA. A positive correlation was found between anti-CarP antibodies and IL-17 in the patients' group. The increased level of IL-17 is suggestive of its possible role in the pathogenesis of CarP positive RA patients.
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Artrite Reumatoide , Citocinas , Humanos , Interleucina-17 , Anticorpos Antiproteína Citrulinada , Fator ReumatoideRESUMO
OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.
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Arterite de Células Gigantes , Humanos , Arterite de Células Gigantes/diagnóstico por imagem , Espessura Intima-Media Carotídea , Reprodutibilidade dos Testes , Estudos Prospectivos , Artérias Temporais/diagnóstico por imagem , Ultrassonografia/métodosRESUMO
Alkaptonuria is a disease often forgotten because of its rarity. Its pathogenic mechanism is the deficiency of one of the enzymes of the tyrosine degradation pathway-homogentisate-1, 2-dioxygenase, which sequelae is accumulation and deposition of its metabolite homogentisic acid in connective tissues and urine. Alkaptonuria presents as a clinical triad-darkening urine upon prolonged exposure to air, pigmentation of connective tissues and debilitating arthropathy. We present a case report of a 67-year old patient with alkaptonuria who presented with the clinical triad, but was mistakenly diagnosed as having ankylosing spondylitis in the past. Currently there is no treatment for the disease hence the management strategy was focused on symptoms control with analgesics, physical therapy, dietary modification, vitamin C supplementation, and joint arthroplasty. Alkaptonuria's clinical features are extensively described in the literature and despite the fact that it is a rare disease, due to the similar radiographic changes with spondyloarthropathies, it should be included in the differential diagnosis in young patients presenting with severe joint involvement. Early recognition of the disease is necessary since its natural evolution is joint destruction leading to significant reduction in the quality of life. Alkaptonuria's articular features in the spine and peripheral tissues are well described using the classical imaging techniques. Musculoskeletal ultrasonography shows a characteristic set of findings in the soft tissues, including synovium, cartilage, tendons and entheses.
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Alcaptonúria , Doenças das Cartilagens , Dioxigenases , Artropatias , Ocronose , Osteoartrite , Espondiloartropatias , Idoso , Alcaptonúria/complicações , Alcaptonúria/diagnóstico , Alcaptonúria/metabolismo , Ácido Ascórbico , Ácido Homogentísico/metabolismo , Humanos , Ocronose/complicações , Ocronose/diagnóstico , Osteoartrite/complicações , Qualidade de Vida , Espondiloartropatias/complicações , TirosinaRESUMO
Systemic sclerosis (SSc) is an autoimmune disease with completely undefined etiology and treatment difficulties. The expression of both protein coding and non-coding RNAs is dysregulated during disease development. We aimed to examine a possible regulatory axis implemented in the control of chitinase-3 like protein 1 (CHI3L1) or YKL-40, an inflammation-associated glycoprotein, shown to be elevated in SSc. A panel of seven miRNAs and three lncRNAs potentially involved in the control of CHI3L1 were selected on the basis of in silico analysis. TagMan assay was used to evaluate the expression levels of miRNAs and RT-qPCR for lncRNAs in white blood cells (WBCs) and plasma from SSc patients and healthy controls. Among the eight screened miRNAs, miR-30e-5p (p = 0.04) and miR-30a-5p (p = 0.01) were significantly downregulated in WBCs and plasma of SSc patients, respectively. On the contrary, the expression of the metastasis associated lung adenocarcinoma transcript 1 (MALAT1) (p = 0.044) and the Nuclear enriched abundant transcript 1 (NEAT1) (p = 0.008) in WBCs was upregulated compared to the controls. Increased levels of MALAT1 and NEAT1 could be associated with the downregulation of miR-30e-5p and miR-30a-5p expression in WBCs and plasma. We present novel data on the involvement of a possible regulatory axis lncRNAs/miR-30e/CHI3L1 in SSc and hypothesize that MALAT1 and NEAT1 could act as miR-30e-5p and miR-30a-5p decoys. This may be a reason for the increased serum levels of CHI3L1 in SSc patients.
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BACKGROUND: Differentiating between seronegative rheumatoid arthritis (RA) and psoriatic arthritis (PsA) presenting only with the involvement of the small joints of the hands can be challenging. Implementing musculoskeletal ultrasound (US) to reveal specific patterns of joint and tendon involvement may have an added value in the management of early arthritis. OBJECTIVE: The aim was to investigate whether a seven-joint US score was able to distinguish between patients with RA and PsA. MATERIALS AND METHODS: One hundred and forty-one patients with RA, 65 patients with PsA, and 45 healthy controls (HC) were included in the current study. US assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joint, second and fifth metatarsophalangeal joint was performed, and the following scores were calculated: synovitis and tenosynovitis/ paratenonitis scores on grayscale ultrasound (GSUS) and on power Doppler (PD) US, erosion score, US7 score. RESULTS: RA patients had significantly higher median scores of GS synovitis, PD synovitis, erosions, and US7 than PsA patients (p < 0.001). PsA patients had significantly higher median scores of GS tenosynovitis/paratenonitis and PD tenosynovitis/paratenonitis (p < 0.001). All US scores were significantly higher for both patient groups as compared to the HC group (p < 0.001). CONCLUSION: Sonographic evaluation by a seven-joint score can be helpful in the differentiation between rheumatoid and psoriatic arthritis.
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Artrite Psoriásica , Artrite Reumatoide , Sinovite , Tenossinovite , Humanos , Artrite Psoriásica/diagnóstico por imagem , Tenossinovite/diagnóstico por imagem , Artrite Reumatoide/diagnóstico por imagem , Articulação do Punho , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.
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Tendões/diagnóstico por imagem , Tendões/patologia , Tenossinovite/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Voluntários Saudáveis , Humanos , Hipertrofia/diagnóstico por imagem , Hipertrofia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Tenossinovite/diagnóstico por imagem , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome. It is a result of uncontrolled hyperactivation of the reticuloendothelial system with a release of a huge amount of proinflammatory cytokines in the bloodstream, causing a cytokine storm. It may be primary due to genetic defects and secondary, triggered by viruses, bacteria, parasites, lymphoproliferative, and autoimmune diseases. We present a rare case of HLH triggered by leishmaniasis. HLH accounts for only about 1% of all leishmaniasis cases. CASE REPORT The patient was a 40-year-old previously healthy woman, who has been diagnosed with secondary HLH caused by leishmaniasis. A chronic Epstein-Barr virus (EBV) infection was initially mistakenly interpreted as a trigger agent, because Leishmania amastigotes, present on the first bone marrow biopsy, were not recognized. The treatment with cyclosporin A and corticosteroids suppressed the cytokine storm and prevented the development of complications. Two months later, because of a reactivation of the disease, the patient was referred to a hematologist. A second bone marrow aspiration was performed, in which numerous Leishmania parasites were finally identified. CONCLUSIONS The aim of this case report is to provide more information about the rare phenomenon of secondary HLH triggered by leishmaniasis. Early recognition of the syndrome and its triggering agents will improve disease outcomes and prevent unnecessary treatment with immunosuppressive drugs.
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Infecções por Vírus Epstein-Barr , Leishmaniose , Linfo-Histiocitose Hemofagocítica , Adulto , Feminino , Herpesvirus Humano 4 , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologiaRESUMO
Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. There is recent evidence that the JAK/STAT signaling pathway is markedly activated in SSc patients. To assess the efficacy and safety of tofacitinib (TOF) on skin and musculoskeletal involvement as compared to methotrexate (MTX) in systemic sclerosis (SSc). In this 52-week pilot study, 66 patients with SSc were enrolled: 33 patients received 5 mg of oral TOF twice a day; 33 received 10 mg of MTX weekly. The proportion of dcSSc and lcSSc patients was similar (dcSSc: 42% TOF group and 36% MTX group; lcSSc: 58% TOF group and 64% MTX group). The primary outcome was the change in the modified Rodnan skin score (mRSS). Secondary outcomes included ultrasound (US) skin thickness and musculoskeletal involvement (US10SSc score). Digital ulcers (DUs) and adverse events (AEs) were documented through the treatment. Both groups had similar characteristics and medians on the outcome measures at baseline. At week 52, the TOF median mRSS was significantly lower than the MTX (p < 0.001) with a mean reduction of 13 points versus MTX 2.57. The mean percent improvement in the TOF group was 44% higher than in the MTX group. TOF median US skin thickness was significantly lower than MTX (p < 0.001), with a mean reduction of 0.31 mm versus 0.075 mm in the MTX group. The US10SSc median score was significantly lower in the TOF group (p = 0.002); mean reduction of 10.21 versus 5.27 in the MTX group. Healing of DUs with no new occurrences was observed in the TOF group. There was no significant difference between the groups in the number of AEs from baseline to week 52. TOF showed greater efficacy than MTX in reducing mRSS, skin thickness and musculoskeletal involvement in SSc and a satisfactory safety profile.