Ashish Chandwani, J. Sankar, Saba Pravez, Neeti Goyal, Rajeev Chugh, Harsh Jain, Nidhi Goel, Abhishek Kumar, Kartik Sivasami, Vivek Vasdev
{"title":"An Enigmatic Link Between Arthritis and Dysphagia in an Elderly Male!","authors":"Ashish Chandwani, J. Sankar, Saba Pravez, Neeti Goyal, Rajeev Chugh, Harsh Jain, Nidhi Goel, Abhishek Kumar, Kartik Sivasami, Vivek Vasdev","doi":"10.1111/1756-185x.70540","DOIUrl":"10.1111/1756-185x.70540","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917540","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}
<p>Recent advances in immunometabolism and rheumatology have highlighted the role of gut-derived signals in modulating joint health. In particular, Yang et al. proposed that osteoarthritis (OA) may be influenced by intestinal bile acid metabolism through a mechanistic cascade involving the gut microbiota, Glycoursodeoxycholic acid (GUDCA), intestinal Farnesoid X receptor (FXR), and Glucagon-like peptide 1 (GLP-1) signaling. This emerging gut-to-joint communication axis invites new thinking about the pathogenesis and treatment of rheumatic diseases.</p><p>The gut microbiome plays a crucial role in regulating systemic immunity and metabolism, primarily through its modulation of the bile acid (BA) pool. It influences the composition and transformation of both primary and secondary bile acids. This process was previously thought to occur only in the liver, but recent studies have shown that gut bacteria also perform these transformations, increasing the diversity of bile acids [<span>1-3</span>]. Secondary bile acids play crucial roles in modulating immune cell function and differentiation, impacting systemic immunity [<span>4</span>]. Recent findings further suggest that bile acids act as immunoregulatory signals in the gut environment, shaping both innate and adaptive immune responses by promoting regulatory T cell differentiation and suppressing pro-inflammatory T helper cell development [<span>5</span>].</p><p>GUDCA is a conjugated bile acid formed by the glycine-conjugation of the secondary bile acid ursodeoxycholic acid (UDCA). FXR, a nuclear receptor expressed in the liver and intestine, plays a vital role in regulating bile acid homeostasis, lipid metabolism, and intestinal barrier function. When antagonized by GUDCA in the ileum, FXR activity is reduced, resulting in upregulation of pro-secretory hormones such as Glucagon-like peptide-1 (GLP-1) from enteroendocrine L-cells [<span>1</span>]. Yan et al. explored this feedback and found that GUDCA-induced inhibition of intestinal FXR significantly boosted GLP-1 levels and improved gut barrier function and glucose metabolism in diabetic mouse models [<span>6</span>].</p><p>GLP-1, predominantly released by intestinal L-cells upon food consumption, while primarily known for its insulinotropic effects, also exerts anti-inflammatory and neuroprotective functions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of therapeutic agents commonly prescribed for managing type 2 diabetes (T2D). Examples include exenatide, liraglutide, and semaglutide. These drugs exert their effects by imitating the activity of the naturally produced hormone GLP-1 [<span>7</span>]. Recent studies suggest that GLP-1RA may reduce joint inflammation through modulation of local immune responses [<span>8, 9</span>]. Yang et al. showed that targeting the gut-joint axis through FXR inhibition and GLP-1 modulation in osteoarthritis models led to pain reduction and improved joint pathology, hinting at the therapeuti
{"title":"Reframing Osteoarthritis Therapy Through the Gut–GUDCA–FXR–GLP1 Pathway: Opportunities and Limitations","authors":"Shangqi Guan, Yifang Mei","doi":"10.1111/1756-185x.70535","DOIUrl":"10.1111/1756-185x.70535","url":null,"abstract":"<p>Recent advances in immunometabolism and rheumatology have highlighted the role of gut-derived signals in modulating joint health. In particular, Yang et al. proposed that osteoarthritis (OA) may be influenced by intestinal bile acid metabolism through a mechanistic cascade involving the gut microbiota, Glycoursodeoxycholic acid (GUDCA), intestinal Farnesoid X receptor (FXR), and Glucagon-like peptide 1 (GLP-1) signaling. This emerging gut-to-joint communication axis invites new thinking about the pathogenesis and treatment of rheumatic diseases.</p><p>The gut microbiome plays a crucial role in regulating systemic immunity and metabolism, primarily through its modulation of the bile acid (BA) pool. It influences the composition and transformation of both primary and secondary bile acids. This process was previously thought to occur only in the liver, but recent studies have shown that gut bacteria also perform these transformations, increasing the diversity of bile acids [<span>1-3</span>]. Secondary bile acids play crucial roles in modulating immune cell function and differentiation, impacting systemic immunity [<span>4</span>]. Recent findings further suggest that bile acids act as immunoregulatory signals in the gut environment, shaping both innate and adaptive immune responses by promoting regulatory T cell differentiation and suppressing pro-inflammatory T helper cell development [<span>5</span>].</p><p>GUDCA is a conjugated bile acid formed by the glycine-conjugation of the secondary bile acid ursodeoxycholic acid (UDCA). FXR, a nuclear receptor expressed in the liver and intestine, plays a vital role in regulating bile acid homeostasis, lipid metabolism, and intestinal barrier function. When antagonized by GUDCA in the ileum, FXR activity is reduced, resulting in upregulation of pro-secretory hormones such as Glucagon-like peptide-1 (GLP-1) from enteroendocrine L-cells [<span>1</span>]. Yan et al. explored this feedback and found that GUDCA-induced inhibition of intestinal FXR significantly boosted GLP-1 levels and improved gut barrier function and glucose metabolism in diabetic mouse models [<span>6</span>].</p><p>GLP-1, predominantly released by intestinal L-cells upon food consumption, while primarily known for its insulinotropic effects, also exerts anti-inflammatory and neuroprotective functions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of therapeutic agents commonly prescribed for managing type 2 diabetes (T2D). Examples include exenatide, liraglutide, and semaglutide. These drugs exert their effects by imitating the activity of the naturally produced hormone GLP-1 [<span>7</span>]. Recent studies suggest that GLP-1RA may reduce joint inflammation through modulation of local immune responses [<span>8, 9</span>]. Yang et al. showed that targeting the gut-joint axis through FXR inhibition and GLP-1 modulation in osteoarthritis models led to pain reduction and improved joint pathology, hinting at the therapeuti","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1756-185x.70535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This systematic review analyzed 123 adult-onset cases of anti-mitochondrial antibody-positive myositis with cardiac evaluation. Cardiac involvement was frequent, often refractory to immunosuppressive therapy, and commonly required electronic cardiac devices, highlighting the need for early recognition and proactive cardiac monitoring in this rare and distinct myositis subtype.
{"title":"Anti-Mitochondrial Antibody-Positive Myositis: Analyses of 123 Adult-Onset Cases With Cardiac Evaluation","authors":"Tomoyuki Mutoh, Mikihiro Takahashi, Hiroshi Fujii","doi":"10.1111/1756-185x.70543","DOIUrl":"10.1111/1756-185x.70543","url":null,"abstract":"<p>This systematic review analyzed 123 adult-onset cases of anti-mitochondrial antibody-positive myositis with cardiac evaluation. Cardiac involvement was frequent, often refractory to immunosuppressive therapy, and commonly required electronic cardiac devices, highlighting the need for early recognition and proactive cardiac monitoring in this rare and distinct myositis subtype.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917597","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}
{"title":"Cat Scratch to Vascular Damage: A Rare Case of Bartonella-Induced Large Vessel Vasculitis","authors":"Hulya Ercan Emreol, Veysel Cam, Ozge Basaran","doi":"10.1111/1756-185x.70541","DOIUrl":"10.1111/1756-185x.70541","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917585","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}
{"title":"Painted Butterfly Rash: The Red Queen Effect in a Rembrandt Portrait","authors":"Hulya Elbe","doi":"10.1111/1756-185x.70536","DOIUrl":"10.1111/1756-185x.70536","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911561","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}
Yi-Hsuan Tu, Hao-Yun Chen, Yun-Cheng Tsai, Ning Yi Fu, An-Ping Huo
<p>Before the advent of biologic therapy of Phase II, methotrexate (MTX) has long served as the cornerstone of systemic treatment for psoriasis and psoriatic arthritis (PsA). Current international guidelines including GRAPPA 2022, EULAR 2023, and APLAR 2025 continue to recommend MTX as the first-line conventional synthetic DMARD in PsA management [<span>1-3</span>]. The TICOPA and SEAM-PsA trials further demonstrated modest but clinically relevant improvements in joint outcomes during the initial treatment phase, supporting MTX's role as an early therapeutic option prior to biologic escalation [<span>4, 5</span>].</p><p>The therapeutic landscape for moderate to severe psoriasis has evolved dramatically in the past two decades. The emergence of targeted biologic therapies, particularly interleukin (IL)-17 and IL-23 inhibitors, has redefined clinical goals, shifting the benchmark of treatment from partial disease control to sustained skin clearance and improved quality of life. These agents offer rapid onset of action, superior efficacy, and more favorable safety profiles compared to conventional systemic treatments.</p><p>Nonetheless, amidst this therapeutic progress, a persistent clinical dilemma remains: Is MTX, a decades-old conventional immunomodulator, still necessary when initiating biologic therapy?</p><p>The question is more than historical—it reflects current debates in clinical practice and guidelines. MTX has traditionally been co-prescribed with tumor necrosis factor (TNF)-α inhibitors to reduce the development of anti-drug antibodies (ADAs) and improve drug persistence. This practice, mainly rooted in rheumatologic data, was extended to psoriasis treatment with limited psoriasis-specific validation. However, newer biologics, including IL-17 and IL-23 inhibitors, have inherently low immunogenicity and high intrinsic drug survival, calling into question the continued relevance of routine MTX co-therapy.</p><p>Historically, the rationale for combining MTX with biologics in psoriasis was threefold: suppressing immunogenicity, prolonging drug survival, and enhancing clinical efficacy. While this logic was initially supported by data from rheumatoid arthritis and early TNFi studies in psoriasis, its relevance to newer biologic agents is increasingly challenged by emerging real-world data and trial evidence.</p><p>A 2024 network meta-analysis of clinical trials in PsA evaluated the comparative efficacy of biologics with and without concomitant MTX. The analysis revealed no significant differences in ACR20/50/70 response rates across TNFi, IL-17, and IL-23 inhibitors between monotherapy and MTX combination groups [<span>6</span>]. These findings undermine the assumption that MTX enhances joint control when added to modern biologics.</p><p>For cutaneous psoriasis, the most compelling data come from a 2025 <i>emulated target trial</i> using data from the BADBIR registry, which compared adalimumab monotherapy versus adalimumab plus MTX in over 1
{"title":"Do Psoriasis Patients on Biologics Need Concomitant Methotrexate? Revisiting the Evidence in the Biologic Era","authors":"Yi-Hsuan Tu, Hao-Yun Chen, Yun-Cheng Tsai, Ning Yi Fu, An-Ping Huo","doi":"10.1111/1756-185x.70542","DOIUrl":"10.1111/1756-185x.70542","url":null,"abstract":"<p>Before the advent of biologic therapy of Phase II, methotrexate (MTX) has long served as the cornerstone of systemic treatment for psoriasis and psoriatic arthritis (PsA). Current international guidelines including GRAPPA 2022, EULAR 2023, and APLAR 2025 continue to recommend MTX as the first-line conventional synthetic DMARD in PsA management [<span>1-3</span>]. The TICOPA and SEAM-PsA trials further demonstrated modest but clinically relevant improvements in joint outcomes during the initial treatment phase, supporting MTX's role as an early therapeutic option prior to biologic escalation [<span>4, 5</span>].</p><p>The therapeutic landscape for moderate to severe psoriasis has evolved dramatically in the past two decades. The emergence of targeted biologic therapies, particularly interleukin (IL)-17 and IL-23 inhibitors, has redefined clinical goals, shifting the benchmark of treatment from partial disease control to sustained skin clearance and improved quality of life. These agents offer rapid onset of action, superior efficacy, and more favorable safety profiles compared to conventional systemic treatments.</p><p>Nonetheless, amidst this therapeutic progress, a persistent clinical dilemma remains: Is MTX, a decades-old conventional immunomodulator, still necessary when initiating biologic therapy?</p><p>The question is more than historical—it reflects current debates in clinical practice and guidelines. MTX has traditionally been co-prescribed with tumor necrosis factor (TNF)-α inhibitors to reduce the development of anti-drug antibodies (ADAs) and improve drug persistence. This practice, mainly rooted in rheumatologic data, was extended to psoriasis treatment with limited psoriasis-specific validation. However, newer biologics, including IL-17 and IL-23 inhibitors, have inherently low immunogenicity and high intrinsic drug survival, calling into question the continued relevance of routine MTX co-therapy.</p><p>Historically, the rationale for combining MTX with biologics in psoriasis was threefold: suppressing immunogenicity, prolonging drug survival, and enhancing clinical efficacy. While this logic was initially supported by data from rheumatoid arthritis and early TNFi studies in psoriasis, its relevance to newer biologic agents is increasingly challenged by emerging real-world data and trial evidence.</p><p>A 2024 network meta-analysis of clinical trials in PsA evaluated the comparative efficacy of biologics with and without concomitant MTX. The analysis revealed no significant differences in ACR20/50/70 response rates across TNFi, IL-17, and IL-23 inhibitors between monotherapy and MTX combination groups [<span>6</span>]. These findings undermine the assumption that MTX enhances joint control when added to modern biologics.</p><p>For cutaneous psoriasis, the most compelling data come from a 2025 <i>emulated target trial</i> using data from the BADBIR registry, which compared adalimumab monotherapy versus adalimumab plus MTX in over 1","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1756-185x.70542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Anti-synthetase syndrome (ASyS) is characterized by the presence of antibodies against aminoacyl transfer RNA (tRNA) synthetase and distinct clinical constellations including interstitial lung disease (ILD), myositis, arthritis, mechanic's hands, fever and raynaud's phenomenon (RP). Since the discovery of anti-histidyl-tRNA synthetase (Anti-Jo1) antibody four decades ago, tremendous progress was made in discovering additional anti-synthetase antibodies [<span>1</span>]. There are 20 different aminoacyl-tRNA synthetase enzymes, and 10 distinct anti-synthetase antibodies (ASA) have been identified so far (Table 1). These antibodies are central to disease classification and may influence clinical phenotypes. There are evolving insights into pathophysiology, clinical heterogeneity, and treatment approaches in ASyS. This article aims to review and discuss the recent research advancements in disease sub-phenotyping, classification and therapeutics in ASyS.</p><p>ASyS exhibits significant clinical heterogeneity with varying disease courses and clinical manifestations among patients. Patients with non-Jo1 ASA were previously reported to have a worse survival than Jo1 patients (10-year cumulative survival of 47% vs. 70%, <i>p</i> < 0.005) by Aggarwal et al. [<span>2</span>], probably related to a delay in diagnosis by 8 months in the non-Jo1 positive patients. However, data from a multicenter registry in Hong Kong did not identify a similar survival difference between Jo1 and non-Jo1 positive patients [<span>3</span>]. Clinical phenotypes might exert a greater impact on survival than the presence of specific ASA. Wu et al. performed cluster analysis on more than 700 ASyS patients from China and identified three unique clinical phenotypes independent of ASA specificity: rapidly-progressive ILD (RP-ILD) cluster (23.7% of patients), dermatomyositis (DM)-like cluster (14.5%) and arthritis cluster (61.8%) [<span>4</span>]. The worst prognosis was observed in the RP-ILD cluster with a 10-year survival rate of 37.0%, compared to 69.5% in the DM-like cluster and 87.4% in the arthritis cluster, but the survival rates were comparable among different ASA. Transcriptomic analysis also revealed distinct gene signatures and biological processes in each cluster. Gene signatures implicated in coagulation and platelet activation were enhanced in the RP-ILD cluster, pathways related to viral infection and interferon-mediated signaling were enriched in the DM-like cluster, and lastly, B cell receptor signaling pathways were upregulated in the arthritis cluster. Whether or not the distinct biological pathways can predict treatment responses to targeted therapy, such as janus kinase inhibitors (JAKi) in the DM-like cluster or anti-CD20 in the arthritis cluster will require further research.</p><p>Apart from predicting prognosis, clinical manifestations are crucial in disease classification though there are controversies on universally accepted classification criteria of
{"title":"Anti-Synthetase Syndrome—Advancing Disease Phenotyping, Classification and Treatment","authors":"Iris Yan Ki Tang, Lijun Liu","doi":"10.1111/1756-185x.70538","DOIUrl":"10.1111/1756-185x.70538","url":null,"abstract":"<p>Anti-synthetase syndrome (ASyS) is characterized by the presence of antibodies against aminoacyl transfer RNA (tRNA) synthetase and distinct clinical constellations including interstitial lung disease (ILD), myositis, arthritis, mechanic's hands, fever and raynaud's phenomenon (RP). Since the discovery of anti-histidyl-tRNA synthetase (Anti-Jo1) antibody four decades ago, tremendous progress was made in discovering additional anti-synthetase antibodies [<span>1</span>]. There are 20 different aminoacyl-tRNA synthetase enzymes, and 10 distinct anti-synthetase antibodies (ASA) have been identified so far (Table 1). These antibodies are central to disease classification and may influence clinical phenotypes. There are evolving insights into pathophysiology, clinical heterogeneity, and treatment approaches in ASyS. This article aims to review and discuss the recent research advancements in disease sub-phenotyping, classification and therapeutics in ASyS.</p><p>ASyS exhibits significant clinical heterogeneity with varying disease courses and clinical manifestations among patients. Patients with non-Jo1 ASA were previously reported to have a worse survival than Jo1 patients (10-year cumulative survival of 47% vs. 70%, <i>p</i> < 0.005) by Aggarwal et al. [<span>2</span>], probably related to a delay in diagnosis by 8 months in the non-Jo1 positive patients. However, data from a multicenter registry in Hong Kong did not identify a similar survival difference between Jo1 and non-Jo1 positive patients [<span>3</span>]. Clinical phenotypes might exert a greater impact on survival than the presence of specific ASA. Wu et al. performed cluster analysis on more than 700 ASyS patients from China and identified three unique clinical phenotypes independent of ASA specificity: rapidly-progressive ILD (RP-ILD) cluster (23.7% of patients), dermatomyositis (DM)-like cluster (14.5%) and arthritis cluster (61.8%) [<span>4</span>]. The worst prognosis was observed in the RP-ILD cluster with a 10-year survival rate of 37.0%, compared to 69.5% in the DM-like cluster and 87.4% in the arthritis cluster, but the survival rates were comparable among different ASA. Transcriptomic analysis also revealed distinct gene signatures and biological processes in each cluster. Gene signatures implicated in coagulation and platelet activation were enhanced in the RP-ILD cluster, pathways related to viral infection and interferon-mediated signaling were enriched in the DM-like cluster, and lastly, B cell receptor signaling pathways were upregulated in the arthritis cluster. Whether or not the distinct biological pathways can predict treatment responses to targeted therapy, such as janus kinase inhibitors (JAKi) in the DM-like cluster or anti-CD20 in the arthritis cluster will require further research.</p><p>Apart from predicting prognosis, clinical manifestations are crucial in disease classification though there are controversies on universally accepted classification criteria of","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1756-185x.70538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The subdivisions of the anterior cingulate cortex (ACC) are involved in distinct functions in the processing of chronic pain and regulation of emotions. However, the specific impact of each ACC subdivision on fibromyalgia (FM) remains unclear. This study aimed to systematically investigate the abnormal resting-state functional connectivity (rsFC) patterns between the ACC (and its subregions) and other chronic-pain-related limbic cortices and subcortical nuclei in patients with FM.
Methods
Resting-state functional magnetic resonance imaging (fMRI) was conducted in 31 patients diagnosed with fibromyalgia (FM) and 32 demographically matched healthy controls (HCs). Using subdivisions of the anterior cingulate cortex (ACC) as regions of interest, we employed a seed-based resting-state functional connectivity (rsFC) approach to identify alterations in connectivity between limbic cortex and subcortical nuclei. A two-sample t-test was applied to compare functional connectivity differences between the two groups. Additionally, Pearson correlation analysis was performed to examine the relationships between rsFC alterations and measures of executive function and clinical symptom severity.
Results
Patients with FM demonstrated aberrant rsFC of the dorsal ACC (dACC) with the limbic system, notably the amygdala (t = 2.840, SE = 0.942, p = 0.007), parahippocampal gyrus (t = 2.340, SE = 0.905, p = 0.024), and insula (t = 2.159, SE = 0.835, p = 0.036). Subregion analyses further revealed heightened connectivity of the anterior midcingulate cortex (aMCC) with the parahippocampal gyrus (t = 2.737, SE = 1.064, p = 0.009), and increased connectivity of the superior anterior cingulate cortex (supACC) with the insula (t = 2.596, SE = 0.706, p = 0.013) and amygdala (t = 2.398, SE = 0.812, p = 0.021), which were significantly associated with pain severity and depressive symptoms in FM.
Conclusion
This study revealed specific abnormalities in the rsFC between the dACC and the limbic cortices and subcortical nuclei in FM patients. The heightened connectivity of the aMCC with the parahippocampal gyrus and of the supACC with the insula and amygdala was closely associated with the regulation of emotion and processing of chronic pain.
目的：前扣带皮层（ACC）的分支在慢性疼痛加工和情绪调节中具有不同的功能。然而，每个ACC细分对纤维肌痛（FM）的具体影响尚不清楚。本研究旨在系统探讨FM患者ACC（及其亚区）与其他慢性疼痛相关边缘皮质和皮质下核之间的异常静息状态功能连接（rsFC）模式。方法：对31例诊断为纤维肌痛（FM）的患者和32例人口统计学匹配的健康对照（hc）进行静息状态功能磁共振成像（fMRI）检查。使用前扣带皮层（ACC）的细分作为感兴趣的区域，我们采用基于种子的静息状态功能连接（rsFC）方法来识别边缘皮层和皮层下核之间连接的变化。采用双样本t检验比较两组之间的功能连接差异。此外，进行Pearson相关分析以检验rsFC改变与执行功能测量和临床症状严重程度之间的关系。结果：FM患者的背侧ACC （dACC）与边缘系统的rsFC均出现异常，尤其是杏仁核（t = 2.840, SE = 0.942, p = 0.007）、海马旁回（t = 2.340, SE = 0.905, p = 0.024）和脑岛（t = 2.159, SE = 0.835, p = 0.036）。亚区分析进一步显示，前扣带皮层（aMCC）与海马旁回的连通性增强（t = 2.737, SE = 1.064, p = 0.009），上扣带前皮层（supACC）与脑岛（t = 2.596, SE = 0.706, p = 0.013）和杏仁核（t = 2.398, SE = 0.812, p = 0.021）的连通性增强，这与FM患者的疼痛程度和抑郁症状显著相关。结论：本研究揭示了FM患者dACC与边缘皮层和皮质下核之间的rsFC的特异性异常。aMCC与海马旁回、supACC与脑岛和杏仁核的高度连通性与情绪调节和慢性疼痛处理密切相关。
{"title":"Abnormal Resting-State Functional Connectivity Between the Dorsal Anterior Cingulate Cortex and the Limbic System Contributes to Pain and Emotion Regulation Impairment in Fibromyalgia Patients","authors":"Yu Wang, Yixin Zhou, Aihui Liu, Chengliang Mao, Shinan Li, Shan Huang, Xingyi Zhu, Hongyang Jiang, Zhenhua Ying","doi":"10.1111/1756-185x.70531","DOIUrl":"10.1111/1756-185x.70531","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The subdivisions of the anterior cingulate cortex (ACC) are involved in distinct functions in the processing of chronic pain and regulation of emotions. However, the specific impact of each ACC subdivision on fibromyalgia (FM) remains unclear. This study aimed to systematically investigate the abnormal resting-state functional connectivity (rsFC) patterns between the ACC (and its subregions) and other chronic-pain-related limbic cortices and subcortical nuclei in patients with FM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Resting-state functional magnetic resonance imaging (fMRI) was conducted in 31 patients diagnosed with fibromyalgia (FM) and 32 demographically matched healthy controls (HCs). Using subdivisions of the anterior cingulate cortex (ACC) as regions of interest, we employed a seed-based resting-state functional connectivity (rsFC) approach to identify alterations in connectivity between limbic cortex and subcortical nuclei. A two-sample <i>t</i>-test was applied to compare functional connectivity differences between the two groups. Additionally, Pearson correlation analysis was performed to examine the relationships between rsFC alterations and measures of executive function and clinical symptom severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with FM demonstrated aberrant rsFC of the dorsal ACC (dACC) with the limbic system, notably the amygdala (<i>t</i> = 2.840, SE = 0.942, <i>p</i> = 0.007), parahippocampal gyrus (<i>t</i> = 2.340, SE = 0.905, <i>p</i> = 0.024), and insula (t = 2.159, SE = 0.835, <i>p</i> = 0.036). Subregion analyses further revealed heightened connectivity of the anterior midcingulate cortex (aMCC) with the parahippocampal gyrus (<i>t</i> = 2.737, SE = 1.064, <i>p</i> = 0.009), and increased connectivity of the superior anterior cingulate cortex (supACC) with the insula (<i>t</i> = 2.596, SE = 0.706, <i>p</i> = 0.013) and amygdala (<i>t</i> = 2.398, SE = 0.812, <i>p</i> = 0.021), which were significantly associated with pain severity and depressive symptoms in FM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study revealed specific abnormalities in the rsFC between the dACC and the limbic cortices and subcortical nuclei in FM patients. The heightened connectivity of the aMCC with the parahippocampal gyrus and of the supACC with the insula and amygdala was closely associated with the regulation of emotion and processing of chronic pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12757978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joban Deol, Deepak Moka, G. S. R. S. N. K. Naidu, Varun Dhir, Shefali Sharma, Aman Sharma, Sanjay Jain
{"title":"Beyond the Surface: The Dual Challenge of Dysphagia and Acrokeratosis","authors":"Joban Deol, Deepak Moka, G. S. R. S. N. K. Naidu, Varun Dhir, Shefali Sharma, Aman Sharma, Sanjay Jain","doi":"10.1111/1756-185x.70533","DOIUrl":"10.1111/1756-185x.70533","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878412","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}
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