Pub Date : 2024-07-15DOI: 10.55563/clinexprheumatol/eeglsa
Julie J Paik, Jiri Vencovský, Christina Charles-Schoeman, Grace C Wright, Ruth Ann Vleugels, Alexandra S Goriounova, Paul N Mudd, Rohit Aggarwal
Dermatomyositis (DM) is a rare and debilitating, systemic, autoimmune disease. While heterogenous in presentation and severity, DM is primarily characterised by a spectrum of skin and muscle disease, which may include proximal muscle weakness and recalcitrant cutaneous eruptions. DM may also be associated with joint pain and stiffness, inflammatory arthritis, dysphagia, fatigue, and calcinosis. The current standard of care for DM includes glucocorticoids, immunosuppressants, and intravenous immunoglobulin (IVIg). Unfortunately, these medications are not uniformly effective and can lead to adverse events, particularly with chronic use, necessitating discontinuation of therapy. Therefore, a substantial unmet need exists for more tailored and efficacious therapies that target DM pathogenesis. Brepocitinib is an oral, once-daily, novel, and specific TYK2/JAK1 inhibitor. Brepocitinib's potent inhibition of TYK2 and JAK1 reduces the signalling of pro-inflammatory cytokines, including IFN-α/β, IL-12, IL-23, and IFNγ, that have been implicated in the pathogenesis of DM. Other JAK inhibitors have been used off-label in both case series and open-label clinical trials in patients with DM; and brepocitinib has demonstrated efficacy in phase 2 clinical trials of several other autoimmune diseases, including plaque psoriasis, psoriatic arthritis, Crohn's disease, hidradenitis suppurativa, and ulcerative colitis. Therefore, there is a strong scientific and clinical rationale for the utility and potential effectiveness of brepocitinib in the treatment of DM patients. Currently, the safety, tolerability, and efficacy of brepocitinib is being evaluated in the largest (n=225) double-blind placebo-controlled phase 3 trial in DM patients to date (VALOR - NCT0543726).
{"title":"Brepocitinib, a potent and selective TYK2/JAK1 inhibitor: scientific and clinical rationale for dermatomyositis.","authors":"Julie J Paik, Jiri Vencovský, Christina Charles-Schoeman, Grace C Wright, Ruth Ann Vleugels, Alexandra S Goriounova, Paul N Mudd, Rohit Aggarwal","doi":"10.55563/clinexprheumatol/eeglsa","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/eeglsa","url":null,"abstract":"<p><p>Dermatomyositis (DM) is a rare and debilitating, systemic, autoimmune disease. While heterogenous in presentation and severity, DM is primarily characterised by a spectrum of skin and muscle disease, which may include proximal muscle weakness and recalcitrant cutaneous eruptions. DM may also be associated with joint pain and stiffness, inflammatory arthritis, dysphagia, fatigue, and calcinosis. The current standard of care for DM includes glucocorticoids, immunosuppressants, and intravenous immunoglobulin (IVIg). Unfortunately, these medications are not uniformly effective and can lead to adverse events, particularly with chronic use, necessitating discontinuation of therapy. Therefore, a substantial unmet need exists for more tailored and efficacious therapies that target DM pathogenesis. Brepocitinib is an oral, once-daily, novel, and specific TYK2/JAK1 inhibitor. Brepocitinib's potent inhibition of TYK2 and JAK1 reduces the signalling of pro-inflammatory cytokines, including IFN-α/β, IL-12, IL-23, and IFNγ, that have been implicated in the pathogenesis of DM. Other JAK inhibitors have been used off-label in both case series and open-label clinical trials in patients with DM; and brepocitinib has demonstrated efficacy in phase 2 clinical trials of several other autoimmune diseases, including plaque psoriasis, psoriatic arthritis, Crohn's disease, hidradenitis suppurativa, and ulcerative colitis. Therefore, there is a strong scientific and clinical rationale for the utility and potential effectiveness of brepocitinib in the treatment of DM patients. Currently, the safety, tolerability, and efficacy of brepocitinib is being evaluated in the largest (n=225) double-blind placebo-controlled phase 3 trial in DM patients to date (VALOR - NCT0543726).</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cardiomyopathies cause most intracardiac thrombosis (ICT), and Behçet's syndrome (BS) is a rare inflammatory disease that can be responsible for a proportion of ICT. Other inflammatory disorders involved in the aetiology of ICT include antiphospholipid syndrome, Henoch-Schonlein purpura, COVID-19, and Loeffler endocarditis. ICT usually occur during the active phase of BS, and they have a close relationship with vascular involvement. Atrial myxomas are benign cardiac tumours arising from the interatrial septum. They can lead to a substantial acute phase response, making them difficult to distinguish from inflammatory diseases. In this case study, we present a 46-year-old female BS patient who presented with constitutional symptoms mimicking BS flare in a routine follow-up visit and was diagnosed with left atrial myxoma after administration of several lines of immunosuppressives. Then, she underwent surgical tumour excision, and a histopathological examination confirmed the diagnosis.In conclusion, atrial myxoma should be kept in mind first of all when suspecting ICT, and advanced imaging methods such as cardiac magnetic resonance imaging (MRI) should be used if necessary.
{"title":"Atrial myxoma as a mimicker of intracardiac thrombus in Behçet's syndrome: a case study with histopathological confirmation.","authors":"Tumay Ak, Bahar Bayrakdar, Sebnem Batur, Emine Sebnem Durmaz, Murat Cimci, Emire Seyahi","doi":"10.55563/clinexprheumatol/j29rnr","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/j29rnr","url":null,"abstract":"<p><p>Cardiomyopathies cause most intracardiac thrombosis (ICT), and Behçet's syndrome (BS) is a rare inflammatory disease that can be responsible for a proportion of ICT. Other inflammatory disorders involved in the aetiology of ICT include antiphospholipid syndrome, Henoch-Schonlein purpura, COVID-19, and Loeffler endocarditis. ICT usually occur during the active phase of BS, and they have a close relationship with vascular involvement. Atrial myxomas are benign cardiac tumours arising from the interatrial septum. They can lead to a substantial acute phase response, making them difficult to distinguish from inflammatory diseases. In this case study, we present a 46-year-old female BS patient who presented with constitutional symptoms mimicking BS flare in a routine follow-up visit and was diagnosed with left atrial myxoma after administration of several lines of immunosuppressives. Then, she underwent surgical tumour excision, and a histopathological examination confirmed the diagnosis.In conclusion, atrial myxoma should be kept in mind first of all when suspecting ICT, and advanced imaging methods such as cardiac magnetic resonance imaging (MRI) should be used if necessary.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.55563/clinexprheumatol/t3mejo
Uzma N Awan, Rizwana S Waraich, Ruqaya Nangrejo, Syed Shahid Noor, Iftikhar A Siddiqui, Kashif Ikram
Objectives: Metabolic factors play significant role in the natural history of knee osteoarthritis (KO). There is a limited understanding of molecular and cellular events that give rise to the disease in patients. This study explored the possible cellular mechanisms by which metabolic syndrome leads to KO.
Methods: This cross-sectional study enrolled 80 subjects with KO who fulfilled the ACR diagnostic criteria and were undergoing total knee replacement surgery. The patients were divided into two groups: KO patients without metabolic syndrome and KO patients with metabolic syndrome.
Results: We hypothesised that metabolic syndrome may accelerate pathogenesis of OA by enhanced RAGE axis in articular cartilage and Infrapatellar fat pad of the knee joint. We have found enhanced protein expression of receptor for advanced glycation end products (RAGE) and its ligands AGEs and HMGB-1 in knee joint tissue of KO patients with metabolic syndrome as compared to KO patients without metabolic syndrome. Further downstream, the gene expression of oxidative stress regulators such as NADPH and inflammation, NFĸB were upregulated in KO patients with MetS as compared to KO patients alone. Higher levels of advanced oxidation products and inflammatory marker IL-17 were exhibited in synovial fluid of KO patients with metabolic syndrome. The enhanced levels of these oxidative stress and inflammatory markers were reflected in the serum of KO patients with metabolic syndrome as well.
Conclusions: We conclude that enhanced function of RAGE axis could be one of the mechanisms by which metabolic syndrome leads to KO.
目的:代谢因素在膝关节骨性关节炎(KO)的自然病史中起着重要作用。目前对导致患者患病的分子和细胞事件的了解还很有限。本研究探讨了代谢综合征导致膝骨关节炎的可能细胞机制:这项横断面研究招募了 80 名符合 ACR 诊断标准并正在接受全膝关节置换手术的 KO 患者。患者被分为两组:结果:我们假设代谢综合征会加速 KO 的发生:我们推测代谢综合征可能会通过增强膝关节软骨和髌下脂肪垫中的 RAGE 轴来加速 OA 的发病机制。与未患代谢综合征的 KO 患者相比,我们发现在代谢综合征 KO 患者的膝关节组织中,高级糖化终产物受体(RAGE)及其配体 AGEs 和 HMGB-1 的蛋白表达增强。在下游,与单独患有代谢综合征的 KO 患者相比,患有代谢综合征的 KO 患者体内氧化应激调节因子(如 NADPH 和炎症因子 NFĸB)的基因表达上调。在代谢综合征 KO 患者的滑液中,高级氧化产物和炎症标志物 IL-17 的水平更高。这些氧化应激和炎症标志物水平的升高也反映在代谢综合征 KO 患者的血清中:我们得出结论:RAGE 轴功能增强可能是代谢综合征导致 KO 的机制之一。
{"title":"RAGE signalling contributes to oxidative stress and inflammation in knee osteoarthritis patients with metabolic syndrome.","authors":"Uzma N Awan, Rizwana S Waraich, Ruqaya Nangrejo, Syed Shahid Noor, Iftikhar A Siddiqui, Kashif Ikram","doi":"10.55563/clinexprheumatol/t3mejo","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/t3mejo","url":null,"abstract":"<p><strong>Objectives: </strong>Metabolic factors play significant role in the natural history of knee osteoarthritis (KO). There is a limited understanding of molecular and cellular events that give rise to the disease in patients. This study explored the possible cellular mechanisms by which metabolic syndrome leads to KO.</p><p><strong>Methods: </strong>This cross-sectional study enrolled 80 subjects with KO who fulfilled the ACR diagnostic criteria and were undergoing total knee replacement surgery. The patients were divided into two groups: KO patients without metabolic syndrome and KO patients with metabolic syndrome.</p><p><strong>Results: </strong>We hypothesised that metabolic syndrome may accelerate pathogenesis of OA by enhanced RAGE axis in articular cartilage and Infrapatellar fat pad of the knee joint. We have found enhanced protein expression of receptor for advanced glycation end products (RAGE) and its ligands AGEs and HMGB-1 in knee joint tissue of KO patients with metabolic syndrome as compared to KO patients without metabolic syndrome. Further downstream, the gene expression of oxidative stress regulators such as NADPH and inflammation, NFĸB were upregulated in KO patients with MetS as compared to KO patients alone. Higher levels of advanced oxidation products and inflammatory marker IL-17 were exhibited in synovial fluid of KO patients with metabolic syndrome. The enhanced levels of these oxidative stress and inflammatory markers were reflected in the serum of KO patients with metabolic syndrome as well.</p><p><strong>Conclusions: </strong>We conclude that enhanced function of RAGE axis could be one of the mechanisms by which metabolic syndrome leads to KO.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.55563/clinexprheumatol/db8p4e
Vicente Aldasoro, Vicky Betech-Antar, Santos Castañeda, Eugenio de Miguel, Juan José Rosales, María José García-Velloso
Objectives: The aim of this study is to analyse the diagnostic value of positron emission tomography (PET) in patients with giant cell arteritis (GCA) despite glucocorticoid (GC) therapy before PET acquisition.
Methods: Consecutive patients with strongly suspected GCA according to 2022 EULAR/ACR criteria were included. The physician diagnosis of GCA after 6 months of follow-up was the gold standard. PET was performed at baseline and 6 months later. In patients with negative results at 60 min, delayed imaging was performed at 180 min.
Results: Twenty-six patients were included with a median (IQR) age of 70.5 (57-88) years. Baseline PET was positive in all but one: 18 patients at 60 min and 7 patients after delayed imaging at 180 min. The median (IQR) GC dose at the time of baseline PET was 45 mg/d (26.2-45) of prednisone equivalent with a median exposure of 14 days (7-76.2). At 6 months of follow-up, PET was performed in 22 patients, with positive results in 16. Delayed imaging was performed in 6 patients due to negative PET at 60 min, with positive results in all cases, despite treatment with GC and/or biological therapy.
Conclusions: In patients on GC therapy, delayed imaging protocols applying procedural recommendations for vascular quantification could improve diagnostic accuracy. Therefore, we suggest performing imaging only at 180 min in patients who have been on GCs for more than 3 days as well as in those with highly suspected GCA but negative findings in baseline PET at 60 min.
研究目的本研究旨在分析正电子发射断层扫描(PET)在巨细胞动脉炎(GCA)患者中的诊断价值,这些患者在 PET 采集前曾接受过糖皮质激素(GC)治疗:方法:根据 2022 年 EULAR/ACR 标准,连续纳入强烈怀疑为 GCA 的患者。随访6个月后医生诊断为GCA是金标准。在基线和6个月后进行PET检查。对于 60 分钟后结果为阴性的患者,则在 180 分钟后进行延迟成像:共纳入 26 名患者,中位(IQR)年龄为 70.5(57-88)岁。除一名患者外,其他患者的基线 PET 均为阳性:其中 18 名患者在 60 分钟时 PET 呈阳性,7 名患者在 180 分钟延迟成像后 PET 呈阳性。基线 PET 时的 GC 剂量中位数(IQR)为 45 毫克/天(26.2-45)泼尼松当量,中位暴露时间为 14 天(7-76.2)。随访 6 个月时,对 22 名患者进行了 PET 检测,其中 16 人检测结果呈阳性。6名患者因60分钟后PET呈阴性而进行了延迟成像,尽管接受了GC和/或生物治疗,但所有病例的结果均为阳性:结论:对于接受 GC 治疗的患者,延迟成像方案应用血管定量的程序建议可提高诊断准确性。因此,我们建议对服用 GC 超过 3 天的患者以及高度怀疑 GCA 但在 60 分钟时基线 PET 结果为阴性的患者仅在 180 分钟时进行成像。
{"title":"Diagnosis of giant cell arteritis by 18F-FDG PET/CT in patients on glucocorticoid therapy: importance of delayed imaging.","authors":"Vicente Aldasoro, Vicky Betech-Antar, Santos Castañeda, Eugenio de Miguel, Juan José Rosales, María José García-Velloso","doi":"10.55563/clinexprheumatol/db8p4e","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/db8p4e","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study is to analyse the diagnostic value of positron emission tomography (PET) in patients with giant cell arteritis (GCA) despite glucocorticoid (GC) therapy before PET acquisition.</p><p><strong>Methods: </strong>Consecutive patients with strongly suspected GCA according to 2022 EULAR/ACR criteria were included. The physician diagnosis of GCA after 6 months of follow-up was the gold standard. PET was performed at baseline and 6 months later. In patients with negative results at 60 min, delayed imaging was performed at 180 min.</p><p><strong>Results: </strong>Twenty-six patients were included with a median (IQR) age of 70.5 (57-88) years. Baseline PET was positive in all but one: 18 patients at 60 min and 7 patients after delayed imaging at 180 min. The median (IQR) GC dose at the time of baseline PET was 45 mg/d (26.2-45) of prednisone equivalent with a median exposure of 14 days (7-76.2). At 6 months of follow-up, PET was performed in 22 patients, with positive results in 16. Delayed imaging was performed in 6 patients due to negative PET at 60 min, with positive results in all cases, despite treatment with GC and/or biological therapy.</p><p><strong>Conclusions: </strong>In patients on GC therapy, delayed imaging protocols applying procedural recommendations for vascular quantification could improve diagnostic accuracy. Therefore, we suggest performing imaging only at 180 min in patients who have been on GCs for more than 3 days as well as in those with highly suspected GCA but negative findings in baseline PET at 60 min.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.55563/clinexprheumatol/sp1d13
Toshiyuki Ota, Shun-Ichiro Ota
Objectives: The early diagnosis of seronegative rheumatoid arthritis (SNRA), characterised by the absence of rheumatoid factor and anti-citrullinated antibody, involves a greater challenge compared to seropositive RA (SPRA). This study aimed to assess the discriminatory potential of anti-human IgG hinge antibodies (AHAs) for patients with early SNRA.
Methods: DMARDs-naive patients with SPRA (n=43), SNRA (n=21), and non-RA (n=49), with disease duration < 2 years, were included. Antigens comprised IgG1 or IgG4 F(ab')2 cleaved by pepsin or MMP-3 and their hinge peptide analogues. Eight IgG anti-hinge antibodies (AHAs) against these antigens were measured in sera from the patients and 58 healthy controls (HCs) using ELISA. Serum CRP and MMP-3 levels, and clinical disease activity index (CDAI), were obtained from medical records. The area under the curve (AUC) obtained from logistic regression and receiver operating characteristic curve analyses were used as a discriminant indicator.
Results: The levels of the IgG AHAs were as follows: SPRA≥SNRA≈non-RA>HC. None of the AHAs were effective in discriminating SNRA from non-RA. However, the combination of MMP-3 and AHAs against IgG4 hinge peptide analogues demonstrated the utility (AUC=0.94). Furthermore, combination of MMP-3, AHAs against IgG1 hinge peptide analogues and CDAI maximally exerted discriminatory power (AUC=0.997).
Conclusions: Specific AHAs in combination with MMP-3 and CDAI are potentially useful to discriminate SNRA from non-RA.
{"title":"Impact of anti-human IgG hinge peptide antibodies on identification of patients with early seronegative rheumatoid arthritis.","authors":"Toshiyuki Ota, Shun-Ichiro Ota","doi":"10.55563/clinexprheumatol/sp1d13","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/sp1d13","url":null,"abstract":"<p><strong>Objectives: </strong>The early diagnosis of seronegative rheumatoid arthritis (SNRA), characterised by the absence of rheumatoid factor and anti-citrullinated antibody, involves a greater challenge compared to seropositive RA (SPRA). This study aimed to assess the discriminatory potential of anti-human IgG hinge antibodies (AHAs) for patients with early SNRA.</p><p><strong>Methods: </strong>DMARDs-naive patients with SPRA (n=43), SNRA (n=21), and non-RA (n=49), with disease duration < 2 years, were included. Antigens comprised IgG1 or IgG4 F(ab')2 cleaved by pepsin or MMP-3 and their hinge peptide analogues. Eight IgG anti-hinge antibodies (AHAs) against these antigens were measured in sera from the patients and 58 healthy controls (HCs) using ELISA. Serum CRP and MMP-3 levels, and clinical disease activity index (CDAI), were obtained from medical records. The area under the curve (AUC) obtained from logistic regression and receiver operating characteristic curve analyses were used as a discriminant indicator.</p><p><strong>Results: </strong>The levels of the IgG AHAs were as follows: SPRA≥SNRA≈non-RA>HC. None of the AHAs were effective in discriminating SNRA from non-RA. However, the combination of MMP-3 and AHAs against IgG4 hinge peptide analogues demonstrated the utility (AUC=0.94). Furthermore, combination of MMP-3, AHAs against IgG1 hinge peptide analogues and CDAI maximally exerted discriminatory power (AUC=0.997).</p><p><strong>Conclusions: </strong>Specific AHAs in combination with MMP-3 and CDAI are potentially useful to discriminate SNRA from non-RA.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Takayasu's arteritis (TAK) is a chronic inflammatory large vessel vasculitis with a grim prognosis due to the excessive risk for cardiovascular (CV) diseases. Its diagnosis relies on radiographic imaging and its differentiation particularly from atherosclerosis could be challenging. Hypothesising that vascular morphology observed in TAK would be comparable to that found in type 2 diabetes mellitus (T2DM), a prototype for advanced atherosclerosis, we compared two disease groups using carotid artery B mode US and shear wave elastography (SWE).
Methods: A total of 72 patients with TAK (63F/9M; mean age: 42.7± 10.0 years) and 74 patients with T2DM (65F/9M; mean age: 50.2± 7.1 years) were studied. Intima-media thickness (IMT), outer diameter and arterial stiffness as assessed by SWE values were measured on the common carotid artery (CCA) and atherosclerotic plaques were recorded. Clinical characteristics, CV risk factors and previous history of CV diseases were determined. Framingham risk score was calculated.
Resuults: Patients with TAK exhibited significantly lower atherosclerotic risk but higher systolic blood pressure (BP) levels compared to those with T2DM. The mean values of CCA IMT, outer diameter, and stiffness were significantly elevated among patients with TAK compared to those with T2DM. Carotid artery plaques were evenly distributed between the study groups, but their anatomical localisation and composition differed significantly. While coronary artery disease (CAD) was more prevalent among T2DM patients, cerebrovascular diseases were more frequent among TAK patients.
Conclusions: Our study revealed distinctive vascular alterations and atherosclerotic changes when compared to advanced atherosclerosis associated with T2DM. Apart from these, higher levels of systolic BP and significantly different distribution of CV diseases between TAK and T2DM also suggest that TAK should be handled with distinct assessment strategies than that employed in conventional atherosclerotic conditions.
目的:高安氏动脉炎(TAK)是一种慢性炎症性大血管炎,由于心血管疾病(CV)风险过高,预后很差。其诊断依赖于放射影像学检查,尤其是与动脉粥样硬化的鉴别具有挑战性。我们假设在 TAK 中观察到的血管形态与 2 型糖尿病(T2DM)(晚期动脉粥样硬化的原型)中发现的血管形态相似,因此使用颈动脉 B 模式 US 和剪切波弹性成像(SWE)对两组疾病进行了比较:共研究了 72 名 TAK 患者(63 女/9 男;平均年龄:42.7± 10.0 岁)和 74 名 T2DM 患者(65 女/9 男;平均年龄:50.2± 7.1 岁)。研究人员测量了颈总动脉(CCA)的内中层厚度(IMT)、外径和以 SWE 值评估的动脉僵化程度,并记录了动脉粥样硬化斑块。确定了临床特征、心血管疾病风险因素和既往心血管疾病史。计算出弗雷明汉风险评分:结果:与T2DM患者相比,TAK患者的动脉粥样硬化风险明显较低,但收缩压(BP)水平较高。与T2DM患者相比,TAK患者颈动脉内中膜厚度、外径和僵硬度的平均值明显升高。研究组之间的颈动脉斑块分布均匀,但其解剖位置和组成却有很大不同。冠状动脉疾病(CAD)在T2DM患者中更为常见,而脑血管疾病在TAK患者中更为常见:结论:我们的研究发现,与 T2DM 相关的晚期动脉粥样硬化相比,TAK 患者的血管改变和动脉粥样硬化变化非常明显。除此以外,TAK 和 T2DM 患者的收缩压水平较高,心血管疾病的分布也明显不同,这也表明,在处理 TAK 时,应采取与传统动脉粥样硬化病症不同的评估策略。
{"title":"Carotid artery ultrasonography and shear wave elastography in Takayasu's arteritis: a comparative analysis with diabetes mellitus.","authors":"Serhat Uysal, Ayse Kalyoncu Ucar, Ayse Ozdede, Esra Fırat Şentürk, Ibrahim Adaletli, Melike Melikoğlu, Izzet Fresko, Mustafa Sait Gonen, Emire Seyahi","doi":"10.55563/clinexprheumatol/gyo8xt","DOIUrl":"10.55563/clinexprheumatol/gyo8xt","url":null,"abstract":"<p><strong>Objectives: </strong>Takayasu's arteritis (TAK) is a chronic inflammatory large vessel vasculitis with a grim prognosis due to the excessive risk for cardiovascular (CV) diseases. Its diagnosis relies on radiographic imaging and its differentiation particularly from atherosclerosis could be challenging. Hypothesising that vascular morphology observed in TAK would be comparable to that found in type 2 diabetes mellitus (T2DM), a prototype for advanced atherosclerosis, we compared two disease groups using carotid artery B mode US and shear wave elastography (SWE).</p><p><strong>Methods: </strong>A total of 72 patients with TAK (63F/9M; mean age: 42.7± 10.0 years) and 74 patients with T2DM (65F/9M; mean age: 50.2± 7.1 years) were studied. Intima-media thickness (IMT), outer diameter and arterial stiffness as assessed by SWE values were measured on the common carotid artery (CCA) and atherosclerotic plaques were recorded. Clinical characteristics, CV risk factors and previous history of CV diseases were determined. Framingham risk score was calculated.</p><p><strong>Resuults: </strong>Patients with TAK exhibited significantly lower atherosclerotic risk but higher systolic blood pressure (BP) levels compared to those with T2DM. The mean values of CCA IMT, outer diameter, and stiffness were significantly elevated among patients with TAK compared to those with T2DM. Carotid artery plaques were evenly distributed between the study groups, but their anatomical localisation and composition differed significantly. While coronary artery disease (CAD) was more prevalent among T2DM patients, cerebrovascular diseases were more frequent among TAK patients.</p><p><strong>Conclusions: </strong>Our study revealed distinctive vascular alterations and atherosclerotic changes when compared to advanced atherosclerosis associated with T2DM. Apart from these, higher levels of systolic BP and significantly different distribution of CV diseases between TAK and T2DM also suggest that TAK should be handled with distinct assessment strategies than that employed in conventional atherosclerotic conditions.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.55563/clinexprheumatol/9c6t1r
Zhi Ye, Ruitian Ma, Chen Li, Zhenhua Ying
{"title":"Which JAKi is better for SAPHO syndrome?","authors":"Zhi Ye, Ruitian Ma, Chen Li, Zhenhua Ying","doi":"10.55563/clinexprheumatol/9c6t1r","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/9c6t1r","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.55563/clinexprheumatol/656se0
Giusyda Tarantino, Rebecca Nicolai, Angela Aquilani, Andrea Tomasini, Antonella Celano, Aurora Pucacco, Silvia Magni-Manzoni, Fabrizio De Benedetti, Emiliano Marasco
Objectives: Methotrexate (MTX) is the most used drug to treat children and adults with arthritis and its use is burdened by adverse effects. The MTX intolerance severity score (MISS) was developed in English to identify patients who are intolerant to MTX. The aim of this study was to translate and validate the MISS in Italian.
Methods: The Italian version of the MISS was developed following the "guidelines for process of cross-cultural adaptation of self-reported measures". The Italian version of the MISS was validated in 125 patients with juvenile idiopathic arthritis (JIA) followed at the Rheumatology Unit of Bambino Gesù Children Hospital. We assessed the construct validity and calculated the internal consistency of the Italian MISS. We performed ROC analysis to assess the overall performance of the Italian MISS.
Results: We translated and adapted the MISS to the Italian language. The Italian MISS showed a very good internal consistency as shown by a Cronbach α of 0.87 (95% CI, 0.84-0.90) and a composite reliability of 0.89 (95% CI, 0.83-0.91).The Cohen's κ was 0.81 (95% CI, 0.71-0.91), suggesting a very good construct validity. The ROC analysis showed an area under the curve (AUC) of 0.97 (95% CI, 0.93-0.99). A threshold of 6 to define intolerant patients, showed a sensitivity of 98.3% and specificity of 81.2%.
Conclusions: We developed the Italian version of the MISS and showed its validity and reliability to identify patients intolerant to MTX in clinical practice and in a research setting.
目的:甲氨蝶呤(MTX)是治疗儿童和成人关节炎最常用的药物,但其不良反应也给使用带来了负担。MTX不耐受严重程度评分(MISS)是用英语开发的,用于识别对MTX不耐受的患者。本研究旨在翻译并验证意大利语版的 MISS:方法:意大利语版的 MISS 是根据 "自我报告测量的跨文化适应过程指南 "开发的。在班比诺-格苏(Bambino Gesù)儿童医院风湿科的 125 名幼年特发性关节炎(JIA)患者中对意大利语版 MISS 进行了验证。我们评估了意大利 MISS 的结构效度,并计算了其内部一致性。我们进行了ROC分析,以评估意大利语MISS的整体表现:我们将 MISS 翻译并调整为意大利语。意大利语 MISS 的 Cronbach α 为 0.87(95% CI,0.84-0.90),综合信度为 0.89(95% CI,0.83-0.91),显示出非常好的内部一致性。ROC分析显示曲线下面积(AUC)为0.97(95% CI,0.93-0.99)。以 6 为阈值定义不耐受患者的灵敏度为 98.3%,特异度为 81.2%:我们开发了意大利版 MISS,并证明了它在临床实践和研究环境中识别 MTX 不耐受患者的有效性和可靠性。
{"title":"Translation and validation in Italian of the methotrexate intolerance severity score for children and adults with arthritis.","authors":"Giusyda Tarantino, Rebecca Nicolai, Angela Aquilani, Andrea Tomasini, Antonella Celano, Aurora Pucacco, Silvia Magni-Manzoni, Fabrizio De Benedetti, Emiliano Marasco","doi":"10.55563/clinexprheumatol/656se0","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/656se0","url":null,"abstract":"<p><strong>Objectives: </strong>Methotrexate (MTX) is the most used drug to treat children and adults with arthritis and its use is burdened by adverse effects. The MTX intolerance severity score (MISS) was developed in English to identify patients who are intolerant to MTX. The aim of this study was to translate and validate the MISS in Italian.</p><p><strong>Methods: </strong>The Italian version of the MISS was developed following the \"guidelines for process of cross-cultural adaptation of self-reported measures\". The Italian version of the MISS was validated in 125 patients with juvenile idiopathic arthritis (JIA) followed at the Rheumatology Unit of Bambino Gesù Children Hospital. We assessed the construct validity and calculated the internal consistency of the Italian MISS. We performed ROC analysis to assess the overall performance of the Italian MISS.</p><p><strong>Results: </strong>We translated and adapted the MISS to the Italian language. The Italian MISS showed a very good internal consistency as shown by a Cronbach α of 0.87 (95% CI, 0.84-0.90) and a composite reliability of 0.89 (95% CI, 0.83-0.91).The Cohen's κ was 0.81 (95% CI, 0.71-0.91), suggesting a very good construct validity. The ROC analysis showed an area under the curve (AUC) of 0.97 (95% CI, 0.93-0.99). A threshold of 6 to define intolerant patients, showed a sensitivity of 98.3% and specificity of 81.2%.</p><p><strong>Conclusions: </strong>We developed the Italian version of the MISS and showed its validity and reliability to identify patients intolerant to MTX in clinical practice and in a research setting.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.55563/clinexprheumatol/aa6drm
AlHanouf Al-Saleem, Shahad Alansari, Mohammed Almuhaizea, Sulaiman M Al-Mayouf
Objectives: IFN-mediated diseases are mendelian innate immunodysregulatory disorders that present early in life with fevers, sterile organ inflammation, and a high type-I IFN-response gene signature in peripheral blood cells. To date, monumental discoveries of novel genetic variants with various phenotypic features have been recognised. We aimed to describe the genotype and phenotype findings in Saudi children diagnosed with autoinflammatory interferonopathy and to report novel findings.
Methods: This is a descriptive retrospective cohort study of children with genetically confirmed type I interferonopathies. Medical records were reviewed for demographic, family history, clinical and laboratory data. All patients underwent genetic testing.
Results: A total of 20 patients (11 females) were included in the study. Sixteen patients (80%) presented within the first 2 years. The median age of disease onset was 0.87 years (IQR: 0.5-2) and the median age of diagnosis was 4.5 years (IQR: 2-7.5). The rates of consanguinity and family history of affected members were high (88% and 47%, respectively). Among the cohort of patients, whole exome sequencing was conducted for 15 patients. Three patients underwent targeted gene tests, and 2 patients had a leukoencephalopathy genetic panel. Eight patients were diagnosed with Aicardi-Goutières syndrome, attributed to variants in the RNASEH2A, RNASEH2C, and IFIH1 genes. Additionally, 2 patients were identified with STING-associated vasculopathy with onset in infancy linked to the TMEM173 variant. One patient exhibited chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature due to PSMB8, and another patient had DNase II. Moreover, 8 patients presented with rare interferonopathy conditions, including three with ISG15, 3 with ZNFX1, 1 with the SOCS1 variant, and 1 the STAT1 variant. Of 12 variants, six (50%) found to have novel genetic variants. The most frequent features were fever (75%), neurology (70%), mucocutaneous (60%), gastrointestinal (50%), and pulmonary (50%). Hypogammaglobinaemia and recurrent infections were seen in (45%) and (20%), respectively. Fifteen patients (75%) had elevated inflammatory markers. The majority of patients received intensive treatment, including corticosteroids, JAK inhibitors, IVIG, and various immunosuppressive agents. Despite these interventions, a partial response to treatment was observed, and cumulative disease damage primarily manifested as growth failure and developmental delay.
Conclusions: Our findings support the previous reports; early-onset fever, neurology, and respiratory features should raise the suspicion of interferonopathies. However, there is eminent evidence of phenotypic variability. Our data also expanded the spectrum of clinical findings in relation to novel genetic variants.
{"title":"Monogenic interferon-mediated diseases: novel phenotype and genotype characteristics from a Saudi population.","authors":"AlHanouf Al-Saleem, Shahad Alansari, Mohammed Almuhaizea, Sulaiman M Al-Mayouf","doi":"10.55563/clinexprheumatol/aa6drm","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/aa6drm","url":null,"abstract":"<p><strong>Objectives: </strong>IFN-mediated diseases are mendelian innate immunodysregulatory disorders that present early in life with fevers, sterile organ inflammation, and a high type-I IFN-response gene signature in peripheral blood cells. To date, monumental discoveries of novel genetic variants with various phenotypic features have been recognised. We aimed to describe the genotype and phenotype findings in Saudi children diagnosed with autoinflammatory interferonopathy and to report novel findings.</p><p><strong>Methods: </strong>This is a descriptive retrospective cohort study of children with genetically confirmed type I interferonopathies. Medical records were reviewed for demographic, family history, clinical and laboratory data. All patients underwent genetic testing.</p><p><strong>Results: </strong>A total of 20 patients (11 females) were included in the study. Sixteen patients (80%) presented within the first 2 years. The median age of disease onset was 0.87 years (IQR: 0.5-2) and the median age of diagnosis was 4.5 years (IQR: 2-7.5). The rates of consanguinity and family history of affected members were high (88% and 47%, respectively). Among the cohort of patients, whole exome sequencing was conducted for 15 patients. Three patients underwent targeted gene tests, and 2 patients had a leukoencephalopathy genetic panel. Eight patients were diagnosed with Aicardi-Goutières syndrome, attributed to variants in the RNASEH2A, RNASEH2C, and IFIH1 genes. Additionally, 2 patients were identified with STING-associated vasculopathy with onset in infancy linked to the TMEM173 variant. One patient exhibited chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature due to PSMB8, and another patient had DNase II. Moreover, 8 patients presented with rare interferonopathy conditions, including three with ISG15, 3 with ZNFX1, 1 with the SOCS1 variant, and 1 the STAT1 variant. Of 12 variants, six (50%) found to have novel genetic variants. The most frequent features were fever (75%), neurology (70%), mucocutaneous (60%), gastrointestinal (50%), and pulmonary (50%). Hypogammaglobinaemia and recurrent infections were seen in (45%) and (20%), respectively. Fifteen patients (75%) had elevated inflammatory markers. The majority of patients received intensive treatment, including corticosteroids, JAK inhibitors, IVIG, and various immunosuppressive agents. Despite these interventions, a partial response to treatment was observed, and cumulative disease damage primarily manifested as growth failure and developmental delay.</p><p><strong>Conclusions: </strong>Our findings support the previous reports; early-onset fever, neurology, and respiratory features should raise the suspicion of interferonopathies. However, there is eminent evidence of phenotypic variability. Our data also expanded the spectrum of clinical findings in relation to novel genetic variants.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.55563/clinexprheumatol/2dsv33
Eva H van Geel, Maarten Boers, Linda Hartman, Yvo M Smulders
Objectives: Glucocorticoids (GC) are important in the treatment of autoinflammatory disorders. Oral prednisolone ≤5 mg/day can be effective, but such doses are at or even below physiological daily endogenous GC production. We hypothesised that their immunosuppressive effect might be explained by high hepatic bioavailability of oral GC, exposing the liver to supraphysiological GC via the portal circulation. We tested this by comparing the effect of oral versus subcutaneous low-dose prednisolone, on erythrocyte sedimentation rate (ESR).
Methods: Patients with rheumatoid arthritis or psoriatic arthritis, elevated ESR (≥30 mm/h) and no current or recent GC therapy were eligible. In a pilot study (n=5), 5 mg/day oral prednisolone decreased ESR significantly, suggesting a sample size of 10 patients for a randomised, non-blinded crossover trial. Patients received 5 mg/day prednisolone for 2 periods of 4 days: one treatment period orally and one subcutaneously with a 10-day washout period between treatments. ESR was measured before (day 1 and 15) and after (day 5 and 19) each treatment course.
Results: 10 patients were included. ESR decreased after both oral and subcutaneous prednisolone, by -5.6 (20.9) and -5.8 (3.0) mm/h, respectively (p=0.98). The treatment order had no effect on the outcome.
Conclusions: . Short-term oral low-dose GC therapy is not more effective than parental GC in decreasing ESR, arguing against therapeutic high hepatic bioavailability effects. More likely, systemic concentration peaks following administration explain why oral physiological steroid doses are clinically effective.
{"title":"Does high hepatic bioavailability enhance the effect of oral compared to subcutaneous glucocorticoids?","authors":"Eva H van Geel, Maarten Boers, Linda Hartman, Yvo M Smulders","doi":"10.55563/clinexprheumatol/2dsv33","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/2dsv33","url":null,"abstract":"<p><strong>Objectives: </strong>Glucocorticoids (GC) are important in the treatment of autoinflammatory disorders. Oral prednisolone ≤5 mg/day can be effective, but such doses are at or even below physiological daily endogenous GC production. We hypothesised that their immunosuppressive effect might be explained by high hepatic bioavailability of oral GC, exposing the liver to supraphysiological GC via the portal circulation. We tested this by comparing the effect of oral versus subcutaneous low-dose prednisolone, on erythrocyte sedimentation rate (ESR).</p><p><strong>Methods: </strong>Patients with rheumatoid arthritis or psoriatic arthritis, elevated ESR (≥30 mm/h) and no current or recent GC therapy were eligible. In a pilot study (n=5), 5 mg/day oral prednisolone decreased ESR significantly, suggesting a sample size of 10 patients for a randomised, non-blinded crossover trial. Patients received 5 mg/day prednisolone for 2 periods of 4 days: one treatment period orally and one subcutaneously with a 10-day washout period between treatments. ESR was measured before (day 1 and 15) and after (day 5 and 19) each treatment course.</p><p><strong>Results: </strong>10 patients were included. ESR decreased after both oral and subcutaneous prednisolone, by -5.6 (20.9) and -5.8 (3.0) mm/h, respectively (p=0.98). The treatment order had no effect on the outcome.</p><p><strong>Conclusions: </strong>. Short-term oral low-dose GC therapy is not more effective than parental GC in decreasing ESR, arguing against therapeutic high hepatic bioavailability effects. More likely, systemic concentration peaks following administration explain why oral physiological steroid doses are clinically effective.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}