|
1
|
Marín-Jiménez I, Carpio D, Hernández V, Muñoz F, Zatarain-Nicolás E, Zabana Y, Mañosa M, Rodríguez-Moranta F, Barreiro-de Acosta M, Gutiérrez Casbas A. Spanish Working Group in Crohn's Disease and Ulcerative Colitis (GETECCU) position paper on cardiovascular disease in patients with inflammatory bowel disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502314. [PMID: 39615874 DOI: 10.1016/j.gastrohep.2024.502314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 11/24/2024] [Indexed: 01/12/2025]
Abstract
Cardiovascular diseases (CVD) are the leading cause of death worldwide. Therefore, it is essential to understand their relationship and prevalence in different diseases that may present specific risk factors for them. The objective of this document is to analyze the specific prevalence of CVD in patients with inflammatory bowel disease (IBD), describing the presence of classical and non-classical cardiovascular risk factors in these patients. Additionally, we will detail the pathophysiology of atherosclerosis in this patient group and the different methods used to assess cardiovascular risk, including the use of risk calculators in clinical practice and different ways to assess subclinical atherosclerosis and endothelial dysfunction. Furthermore, we will describe the potential influence of medication used for managing patients with IBD on cardiovascular risk, as well as the potential influence of commonly used drugs for managing CVD on the course of IBD. The document provides comments and evidence-based recommendations based on available evidence and expert opinion. An interdisciplinary group of gastroenterologists specialized in IBD management, along with a consulting cardiologist for this type of patients, participated in the development of these recommendations by the Spanish Group of Work on Crohn's Disease and Ulcerative Colitis (GETECCU).
Collapse
Affiliation(s)
- Ignacio Marín-Jiménez
- Sección de Gastroenterología, Servicio de Aparato Digestivo, Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España.
| | - Daniel Carpio
- Servicio de Aparato Digestivo, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, España; Grupo de Investigación en Hepatología-Enfermedades Inflamatorias Intestinales, Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Pontevedra, España
| | - Vicent Hernández
- Servicio de Aparato Digestivo, Complexo Hospitalario Universitario de Vigo (CHUVI), SERGAS, Vigo, Pontevedra, España; Grupo de Investigación en Patología Digestiva, Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Pontevedra, España
| | - Fernando Muñoz
- Servicio de Digestivo. Complejo Asistencial Universitario de Salamanca, Salamanca, España
| | - Eduardo Zatarain-Nicolás
- Servicio de Cardiología, Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid; CIBERCV, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Universidad Complutense de Madrid, Madrid, España
| | - Yamile Zabana
- Servicio de Aparato Digestivo, Hospital Universitari Mútua Terrassa; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Terrasa, Barcelona, España
| | - Míriam Mañosa
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Barcelona, España
| | - Francisco Rodríguez-Moranta
- Servicio de Aparato Digestivo, Hospital Universitario de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, España
| | - Manuel Barreiro-de Acosta
- Servicio de Gastroenterología, Hospital Clínico Universitario de Santiago, A Coruña, España; Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña, España
| | - Ana Gutiérrez Casbas
- Servicio Medicina Digestiva, Hospital General Universitario Dr Balmis de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), CIBERehd, Alicante, España
| |
Collapse
|
|
2
|
Lin S, Jensen MD. Human Adipose Tissue Metabolism in Obesity. J Obes Metab Syndr 2025; 34:105-119. [PMID: 40194889 PMCID: PMC12066998 DOI: 10.7570/jomes25025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Revised: 03/21/2025] [Accepted: 03/21/2025] [Indexed: 04/09/2025] Open
Abstract
The scientific understanding of adipose tissue has advanced tremendously during the past decade. Once thought to be an inert fat storage organ, we now know that adipose tissue serves important functions in energy balance and endocrinology, as well as playing a central role in the development of metabolic diseases. Adipose tissue lipid storage and lipolysis are tightly controlled by hormones, such as insulin, in response to the body's energy needs. Adipose insulin sensitivity can be measured in vivo in humans using isotopic fatty acid tracers and the insulin clamp technique. These data allow investigators to calculate the plasma insulin concentration that results in a 50% suppression of lipolysis. In obesity, insulin's action on adipose tissue lipolysis is clearly impaired, resulting in excess free fatty acids in circulation, which can lead to metabolic dysfunction. However, the cause of this impairment is unclear. The chronic, low-grade adipose tissue inflammation seen in obesity was thought to be the cause of adipose tissue insulin resistance. In this review, we discuss the structure of adipose tissue, how normal and abnormal adipose tissue metabolism contributes to metabolic diseases, and how inflammation might or might not play a role in adipose tissue insulin resistance.
Collapse
Affiliation(s)
- Shuhao Lin
- Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
| | | |
Collapse
|
|
3
|
Avouac J, Ait-Oufella H, Habauzit C, Benkhalifa S, Combe B. The Cardiovascular Safety of Tumour Necrosis Factor Inhibitors in Arthritic Conditions: A Structured Review with Recommendations. Rheumatol Ther 2025; 12:211-236. [PMID: 40019616 PMCID: PMC11920476 DOI: 10.1007/s40744-025-00753-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 02/13/2025] [Indexed: 03/01/2025] Open
Abstract
There is accumulating evidence that inflammation is a key driver of atherosclerosis development and thrombotic complications. This pathophysiological mechanism explains, at least in part, the increased cardiovascular risk of patients with immune-mediated arthritis. Experimental and clinical studies have shown that tumour necrosis factor (TNF) plays a pathological role in both vascular and joint diseases, suggesting that TNF inhibitors (TNFis) may limit cardiovascular events in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or spondyloarthritis (SpA). This review summarizes studies exploring the effects of TNFis on cardiovascular outcomes in patients with RA, PsA or SpA. Clinical studies suggest that TNFis reduce vascular inflammation and may improve (or prevent worsening of) endothelial dysfunction and arterial stiffness. There is evidence that TNFis reduce the incidence of cardiovascular events in patients with inflammatory arthritis compared with non-biological treatments, particularly in patients with rheumatoid arthritis. Fewer studies have compared the effects of different classes of biological therapy on outcomes, but found no significant difference in the risk of cardiovascular events between patients taking TNFis and other biological therapy. In contrast, patients at high cardiovascular risk may derive greater benefit from a TNFi than from a Janus kinase inhibitor (JAKi). The cardiovascular impact of JAKis is still under debate, with a recent safety warning. Targeted control of inflammation is a key strategy to reduce the risk of major adverse cardiovascular events in patients with inflammatory arthritis. Cardiovascular evaluation and risk stratification, using a multidisciplinary approach involving rheumatology and cardiology teams, are recommended to guide optimal immunomodulatory treatment.
Collapse
Affiliation(s)
- Jérôme Avouac
- Service de Rhumatologie, Hôpital Cochin, AP-HP, Centre-Université Paris Cité, Université de Paris, 27 Rue du Faubourg Saint-Jacques, 75014, Paris, France.
| | - Hafid Ait-Oufella
- INSERM U970, Paris Cardiovascular Research Center, Université Paris Cité, Paris, France
- Service de Médecine Intensive-Réanimation, Hôpital Saint-Antoine, AP-HP, Sorbonne Université, Paris, France
| | | | | | | |
Collapse
|
|
4
|
Smith A, Karahasan A, Yi D, Yapabandara S, Elhindi J, Fernandez-Penas P, Chow C, Zaman S. Biologic Therapy and Cardiometabolic Risk in Psoriasis: A Retrospective Review. Dermatol Ther (Heidelb) 2025; 15:201-212. [PMID: 39843708 PMCID: PMC11785865 DOI: 10.1007/s13555-024-01327-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 12/11/2024] [Indexed: 01/24/2025] Open
Abstract
INTRODUCTION Psoriasis is a systemic inflammatory disease with increased cardiometabolic risk including dyslipidaemia and diabetes. Biologic therapy effectively treats the cutaneous inflammatory burden of psoriasis and evolving evidence suggests potential to reduce systemic inflammatory sequalae that can elevate cardiovascular risk. This study aimed to assess the change in cardiometabolic risk markers in a cohort of patients with psoriasis treated with 1 year of continuous biologic treatment. METHODS A retrospective review was conducted of patients receiving biologic therapy for chronic plaque psoriasis in a single dermatology centre at a major tertiary hospital in Sydney, Australia. The effect of biologic therapy on psoriasis was assessed using the psoriasis area severity index (PASI). Cardiometabolic risk markers assessed included lipid profile (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and haemoglobin A1c (HbA1c). Measurements at baseline and 1 year were compared using paired t tests for analysis of the parameters which approximated normal distribution (TC, LDL, HDL) and Wilcoxon signed-rank test for analysis of those which did not (TG, HbA1c, PASI). Two-tailed P values < 0.05 were considered significant. RESULTS A total of 200 patients were reviewed, of which 39 had complete data sets. The participants' ages ranged from 21 to 85 years (mean 51, SD 16.9). Of the 39 participants, 31 (79.5%) were male, 8 (20.5%) were female; 26 (67%) were biologic experienced (BE) and 13 (33%) were biologic naïve (BN). The mean PASI at baseline (for BN + BE) was 13.4 (SD 9.8). The biologic agents used, according to frequency, included risankizumab, with 14 participants (35.9%), secukinumab by 7 (17.9%), ustekinumab by 6 (15.4%), ixekizumab by 6 (15.4%), guselkumab by 3 (7.7%), infliximab by 2 (5.1%), and adalimumab by 1 (2.6%). After 12 months, significant skin improvement was seen [PASI reduced from 13.43 (SD 9.8) to 1.1 (SD 2.1), p < 0.001]. There was no significant change in lipid profile, including TC (mean difference - 0.1 mmol/L, p = 0.532), LDL-C (mean difference = - 0.1 mmol/L, p = 0.476), HDL (mean difference = - 0.1 mmol/L, p = 0.125), triglycerides (mean difference = 0.0 mmol/l, p = 0.748) or HbA1c (mean difference 0.38%, p = 0.468). CONCLUSION Markers of cardiometabolic risk (lipid profile and HbA1c) did not significantly improve after 1 year of biologic therapy despite significant reduction in psoriasis skin severity. Further research in larger cohorts is needed to elucidate the benefits, if any, of biologic therapy on cardiometabolic parameters in individuals with psoriasis, in order to optimise care for this vulnerable cohort.
Collapse
Affiliation(s)
- Annika Smith
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia.
- Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
- Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
| | - Aidin Karahasan
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia
- Research and Education Network, Western Sydney Local Health District, Sydney, NSW, Australia
| | - Deborah Yi
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia
- Research and Education Network, Western Sydney Local Health District, Sydney, NSW, Australia
| | - Sanjay Yapabandara
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia
- Research and Education Network, Western Sydney Local Health District, Sydney, NSW, Australia
| | - James Elhindi
- Research and Education Network, Western Sydney Local Health District, Sydney, NSW, Australia
| | - Pablo Fernandez-Penas
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia
- Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Clara Chow
- Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia
| | - Sarah Zaman
- Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia
| |
Collapse
|
|
5
|
Ren Z, He L, Wang J, Shu L, Li C, Ma Y. The harmful effect of ankylosing spondylitis on diabetes mellitus: new evidence from the Mendelian randomization analysis. Front Endocrinol (Lausanne) 2024; 15:1369466. [PMID: 39649224 PMCID: PMC11624504 DOI: 10.3389/fendo.2024.1369466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 10/30/2024] [Indexed: 12/10/2024] Open
Abstract
Background While observational research has highlighted a possible link between ankylosing spondylitis (AS) and type 2 diabetes (T2DM), the quality of evidence remains limited, and the causal relationship is yet to be established. This study aims to explore the causal link between AS and T2DM, as well as its impact on traits related to glucose metabolism. Method To infer a causal relationship between AS and various diabetes-related traits, including type 1 diabetes (T1DM), T2DM, blood glucose levels, fasting glucose, glycated hemoglobin, and fasting insulin, we employed Mendelian randomization (MR) analysis. We sourced GWAS summary data for both exposure and outcome variables from the IEU OpenGWAS database, GWAS Catalog, and FinnGen database. To synthesize the results of the MR analyses, we applied meta-analysis techniques using either a fixed or random effects model. For identifying and excluding instrumental variants (IVs) that exhibit horizontal pleiotropy with the outcomes, we utilized the MR-PRESSO method. Sensitivity analyses were conducted using the MR-Egger method, along with Q and I^2 tests, to ensure the robustness of our findings. Results Our analysis revealed a significant association between AS and an increased risk of T1DM with an odds ratio (OR) of 1.5754 (95% CI: 1.2935 to 1.9187) and T2DM with an OR of 1.0519 (95% CI: 1.0059 to 1.1001). Additionally, AS was associated with elevated levels of fasting glucose (beta coefficient = 0.0165, 95% CI: 0.0029 to 0.0301) and blood glucose (beta coefficient = 0.0280, 95% CI: 0.0086 to 0.0474), alongside a decrease in fasting insulin levels (beta coefficient = -0.0190, 95% CI: -0.0330 to -0.0050). Conclusion Our findings collectively underscore the detrimental impact of AS on the development of diabetes, highlighting the critical influence of autoimmune disorders in diabetes onset. This provides profound insights into the pathogenesis of diabetes from an immunological standpoint.
Collapse
Affiliation(s)
- Zheng Ren
- Xinjiang Institute of Spinal Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Liang He
- Institute of General Surgery, Wulumuqi General Hospital of People’s Liberation Army (PLA), Urumqi, China
| | - Jing Wang
- Xinjiang Institute of Spinal Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Li Shu
- Xinjiang Institute of Spinal Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Chenyang Li
- Micro Operation of the Third People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Yuan Ma
- Xinjiang Institute of Spinal Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| |
Collapse
|
|
6
|
Fedorchenko Y, Mahmudov K, Abenov Z, Zimba O, Yessirkepov M. Diabetes mellitus in rheumatic diseases: clinical characteristics and treatment considerations. Rheumatol Int 2023; 43:2167-2174. [PMID: 37718369 DOI: 10.1007/s00296-023-05453-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 08/30/2023] [Indexed: 09/19/2023]
Abstract
New pathophysiological insights are now available on comorbidities in rheumatic diseases (RDs). Several nationwide studies point to the fact that comorbid diabetes mellitus (DM) increases the risk of adverse outcomes in patients with various RDs. Genetic factors, intensity of systemic inflammation, anti-inflammatory potential of therapeutic agents, and duration of RDs have been insufficiently explored in the context of comorbidities. Some disease-modifying antirheumatic drugs (DMARDs) have demonstrated a potential to improve the glycemic control while glucocorticoids (GCs) have worsened it, particularly in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Anti-TNFalpha agents in combination with hydroxychloroquine (HCQ) have been associated with a reduced risk of DM in patients with RA, ankylosing spondylitis (AS), Sjögren syndrome (SS), and SLE. Better understanding of confounding factor of currently available antirheumatic therapies in patients with DM and RDs will pave the way for a tailored approach, limiting the severity of clinical manifestations and reducing the mortality risk.
Collapse
Affiliation(s)
- Yuliya Fedorchenko
- Department of Pathophysiology, Ivano-Frankivsk National Medical University, Halytska Str. 2, Ivano-Frankivsk, 76018, Ukraine.
| | - Khaiyom Mahmudov
- Department of Propaedeutics of Internal Diseases, Avicenna Tajik State Medical University, Dushanbe, Tajikistan
| | - Zhumabek Abenov
- Student Polyclinic, Shymkent, Kazakhstan
- South Kazakhstan Medical Academy, Shymkent, Kazakhstan
| | - Olena Zimba
- Department of Clinical Rheumatology and Immunology, University Hospital in Krakow, Krakow, Poland
- National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
- Department of Internal Medicine N2, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Marlen Yessirkepov
- Department of Biology and Biochemistry, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
| |
Collapse
|
|
7
|
Vafaeipour Z, Ghasemzadeh Rahbardar M, Hosseinzadeh H. Effect of saffron, black seed, and their main constituents on inflammatory cytokine response (mainly TNF-α) and oxidative stress status: an aspect on pharmacological insights. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:2241-2259. [PMID: 37103518 DOI: 10.1007/s00210-023-02501-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 04/15/2023] [Indexed: 04/28/2023]
Abstract
Tumor necrosis factor-α (TNF-α), an inflammatory cytokine, is produced by monocytes and macrophages. It is known as a 'double-edged sword' because it is responsible for advantageous and disadvantageous events in the body system. The unfavorable incident includes inflammation, which induces some diseases such as rheumatoid arthritis, obesity, cancer, and diabetes. Many medicinal plants have been found to prevent inflammation, such as saffron (Crocus sativus L.) and black seed (Nigella sativa). Therefore, the purpose of this review was to assess the pharmacological effects of saffron and black seed on TNF-α and diseases related to its imbalance. Different databases without time limitations were investigated up to 2022, including PubMed, Scopus, Medline, and Web of Science. All the original articles (in vitro, in vivo, and clinical studies) were collected on the effects of black seed and saffron on TNF-α. Black seed and saffron have therapeutic effects against many disorders, such as hepatotoxicity, cancer, ischemia, and non-alcoholic fatty liver, by decreasing TNF-α levels based on their anti-inflammatory, anticancer, and antioxidant properties. Saffron and black seed can treat a variety of diseases by suppressing TNF-α and exhibiting a variety of activities such as neuroprotective, gastroprotective, immunomodulatory, antimicrobial, analgesic, antitussive, bronchodilator, antidiabetic activity, anticancer, and antioxidant effects. To uncover the beneficial underlying mechanisms of black seed and saffron, more clinical trials and phytochemical research are required. Also, these two plants affect other inflammatory cytokines, hormones, and enzymes, implying that they could be used to treat a variety of diseases.
Collapse
Affiliation(s)
- Zeinab Vafaeipour
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Hossein Hosseinzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
8
|
Hsieh SC, Tsai PH, Kuo CF, Cheng TT, Lai NS, Lin JC, Lin LH, Tsai CY. Health-related quality of life improvement by adalimumab therapy in patients with rheumatoid arthritis in Taiwan: A nationwide prospective study. J Chin Med Assoc 2023; 86:366-374. [PMID: 36692418 DOI: 10.1097/jcma.0000000000000889] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND To determine the effects of adalimumab on health-related quality of life (HRQoL) in Taiwanese patients with moderate-to-severe rheumatoid arthritis (RA) (NCT02616380). METHODS During a 24-week observational period, 100 biologic-naive patients with RA received 40 mg adalimumab subcutaneously, every 2 weeks. The primary endpoint was a change in Health Assessment Questionnaire-Disability Index (HAQ-DI) score at 24 weeks. The secondary endpoints included change in HAQ-DI at week 12, number and percentage of patients achieving a meaningful improvement in HAQ-DI at weeks 12 and 24, and changes in the 36-Item Short Form Health Survey (SF-36), EuroQol 5-dimension 3-level version (EQ-5D-3L) index, and Work Productivity and Activity Impairment (WPAI) questionnaire scores at weeks 12 and 24. RESULTS At weeks 12 and 24, mean changes in HAQ-DI from baseline were -0.34 ± 0.46 and -0.44 ± 0.59 (both p < 0.001), and clinically meaningful improvement in HAQ-DI was achieved by 60.4% and 59.6% of patients, respectively. SF-36, EQ-5D-3L index, and WPAI scores significantly improved ( p < 0.001) from baseline to weeks 12 and 24. Exploratory analyses showed diabetes was significantly associated with changes in HAQ-DI, EQ-5D-3L, and WPAI scores whereas peptic ulcer correlated with changes in the SF-36 physical component summary T-score. CONCLUSION HRQoL improved after initiation of adalimumab therapy in Taiwanese patients with moderate-to-severe RA.
Collapse
Affiliation(s)
- Song-Chou Hsieh
- Division of Rheumatology, Immunology & Allergy, Department of Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC
| | - Ping-Han Tsai
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan, ROC
| | - Chang-Fu Kuo
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Tien-Tsai Cheng
- Division of Rheumatology, Allergy, and Immunology, Chang Gung University and Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
| | - Ning-Sheng Lai
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan, ROC
| | - Jing-Chi Lin
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan, ROC
| | - Liang-Hung Lin
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, ROC
| | - Chang-Youh Tsai
- Division of Immunology and Rheumatology, Department of Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan, ROC
| |
Collapse
|
|
9
|
Rochette E, Saidi O, Merlin É, Duché P. Physical activity as a promising alternative for young people with juvenile idiopathic arthritis: Towards an evidence-based prescription. Front Immunol 2023; 14:1119930. [PMID: 36860845 PMCID: PMC9969142 DOI: 10.3389/fimmu.2023.1119930] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 01/31/2023] [Indexed: 02/17/2023] Open
Abstract
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in young people. Although biologics now enable most children and adolescents with JIA to enjoy clinical remission, patients present lower physical activity and spend more time in sedentary behavior than their healthy counterparts. This impairment probably results from a physical deconditioning spiral initiated by joint pain, sustained by apprehension on the part of both the child and the child's parents, and entrenched by lowered physical capacities. This in turn may exacerbate disease activity and lead to unfavorable health outcomes including increased risks of metabolic and mental comorbidities. Over the past few decades, there has been growing interest in the health benefits of increased overall physical activity as well as exercise interventions in young people with JIA. However, we are still far from evidence-based physical activity and / or exercise prescription for this population. In this review, we give an overview of the available data supporting physical activity and / or exercise as a behavioral, non-pharmacological alternative to attenuate inflammation while also improving metabolism, disease symptoms, poor sleep, synchronization of circadian rhythms, mental health, and quality of life in JIA. Finally, we discuss clinical implications, identify gaps in knowledge, and outline a future research agenda.
Collapse
Affiliation(s)
- Emmanuelle Rochette
- Department of Pediatrics, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
- Clermont Auvergne University, INSERM, CIC 1405, CRECHE unit, Clermont-Ferrand, France
- Toulon University, Laboratory “Impact of Physical Activity on Health” (IAPS), Toulon, France
| | - Oussama Saidi
- Toulon University, Laboratory “Impact of Physical Activity on Health” (IAPS), Toulon, France
| | - Étienne Merlin
- Department of Pediatrics, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
- Clermont Auvergne University, INSERM, CIC 1405, CRECHE unit, Clermont-Ferrand, France
| | - Pascale Duché
- Toulon University, Laboratory “Impact of Physical Activity on Health” (IAPS), Toulon, France
| |
Collapse
|
|
10
|
Wu D, Luo Y, Li T, Zhao X, Lv T, Fang G, Ou P, Li H, Luo X, Huang A, Pang Y. Systemic complications of rheumatoid arthritis: Focus on pathogenesis and treatment. Front Immunol 2022; 13:1051082. [PMID: 36618407 PMCID: PMC9817137 DOI: 10.3389/fimmu.2022.1051082] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 12/09/2022] [Indexed: 12/24/2022] Open
Abstract
As a systemic autoimmune disease, rheumatoid arthritis (RA) usually causes damage not only to joints, but also to other tissues and organs including the heart, kidneys, lungs, digestive system, eyes, skin, and nervous system. Excessive complications are closely related to the prognosis of RA patients and even lead to increased mortality. This article summarizes the serious complications of RA, focusing on its incidence, pathogenesis, clinical features, and treatment methods, aiming to provide a reference for clinicians to better manage the complications of RA.
Collapse
Affiliation(s)
- Di Wu
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Yehao Luo
- School of Second Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Tong Li
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Xinyi Zhao
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Ting Lv
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Gang Fang
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Peiqi Ou
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Hongyi Li
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Xiaofan Luo
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - An Huang
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China,*Correspondence: An Huang, ; Yuzhou Pang,
| | - Yuzhou Pang
- Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, China,*Correspondence: An Huang, ; Yuzhou Pang,
| |
Collapse
|
|
11
|
Zhou Y, Xie W, Wang L, Zhu X, Li J, Liu L, Zhu S, Wang L. Anti-tumor Necrosis Factor-Alpha Therapy and Hypoglycemia: A Real-World Pharmacovigilance Analysis. Drug Saf 2022; 45:951-959. [PMID: 35857191 DOI: 10.1007/s40264-022-01210-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/29/2022] [Indexed: 12/23/2022]
Abstract
INTRODUCTION An association between tumor necrosis factor (TNF)-α inhibitors and hypoglycemia has been detected in a few case reports and small case series; however, no relevant pharmacovigilance data have been published yet. OBJECTIVE The objective of this study was to detect and characterize relevant safety signals between hypoglycemia and TNF-α inhibitor use. METHODS Indication-focused disproportionality analysis was conducted to detect increased reporting of TNF-α-associated hypoglycemia compared with all other reports with the same indication during the same time period. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated to determine disproportionality. To reduce potential confounding factors, adjusted RORs were further calculated by logistic regression to control for age, sex, diabetes status, and concomitant drugs that potentially affect blood glucose levels. RESULTS In all, 1086 adverse drug reactions related to TNF-α inhibitors were reported as 'hypoglycemia'. There were no disproportionality signals of hypoglycemia in TNF-α inhibitor users with indication of inflammatory bowel disease. When TNF-α inhibitors were considered as a class, disproportion for hypoglycemia only emerged in indication of psoriasis (n = 267, ROR 1.20, 95% CI 1.02-1.41). In further analyses of specific TNF-α inhibitor type, significant RORs for hypoglycemia were found in indication of rheumatic disease, including adalimumab in ankylosing spondylitis (n = 37, ROR 1.97, 95% CI 1.28-3.04), psoriasis (n = 160, ROR 1.64, 95% CI 1.37-1.97), and rheumatoid arthritis (n = 230, ROR 1.35, 95% CI 1.16-1.56) and infliximab in psoriasis (n = 18, ROR 2.14, 95% CI 1.33-3.42). After adjusting for confounding factors, only the signals of adalimumab were stable. CONCLUSIONS Our study identified some potential pharmacovigilance signals between hypoglycemia and TNF-α inhibitors, which warrants further validation.
Collapse
Affiliation(s)
- Yu Zhou
- Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Wenhuo Xie
- Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Linyao Wang
- Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Xinyan Zhu
- Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Jianbin Li
- Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Libin Liu
- Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Shuaijun Zhu
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China.
| | - Lijing Wang
- Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, China.
| |
Collapse
|
|
12
|
Wang CR, Tsai HW. Autoimmune liver diseases in systemic rheumatic diseases. World J Gastroenterol 2022; 28:2527-2545. [PMID: 35949355 PMCID: PMC9254143 DOI: 10.3748/wjg.v28.i23.2527] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/11/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
Systemic rheumatic diseases (SRDs) are chronic, inflammatory, autoimmune disorders with the presence of autoantibodies that may affect any organ or system. Liver dysfunction in SRDs can be associated with prescribed drugs, viral hepatitis, alternative hepatic comorbidities and coexisting autoimmune liver diseases (AILDs), requiring an exclusion of secondary conditions before considering liver involvement. The patterns of overlap diseases depend predominantly on genetic determinants with common susceptible loci widely distributing in both disorders. In AILDs, it is important to identify the overlapping SRDs at an early stage since such a coexistence may influence the disease course and prognosis. Commonly co-occurring SRDs in AILDs are Sjögren syndrome (SS), rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in autoimmune hepatitis (AIH), and SS, RA or systemic sclerosis in primary biliary cholangitis. Owing to different disease complications and therapies, it is imperative to differentiate between SLE liver involvement and SLE-AIH overlap disease. Therapeutic options can be personalized to control coexisting conditions of liver autoimmunity and rheumatic manifestations in AILD-SRD overlap diseases. The collaboration between hepatologists and rheumatologists can lead to significant advances in managing such a complex scenario. In this review, we provide a comprehensive overview on coexisting AILDs in different SRDs and the therapeutic approach in managing these overlap diseases.
Collapse
Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| |
Collapse
|
|
13
|
Wang CR, Tsai HW. Immediate-release tofacitinib reduces insulin resistance in non-diabetic active rheumatoid arthritis patients: A single-center retrospective study. World J Diabetes 2022; 13:454-465. [PMID: 35800413 PMCID: PMC9210542 DOI: 10.4239/wjd.v13.i6.454] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 04/18/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND An increased risk of insulin resistance (IR) has been identified in rheumatoid arthritis (RA), a chronic inflammatory disorder with elevated levels of pathogenic cytokines. Biologics targeting proinflammatory cytokines can control the disease and improve insulin sensitivity in RA. Although Janus kinase (JAK) signaling can regulate cytokine receptors and participate in RA pathogenesis, it remains to be elucidated whether there is a reduction of IR in such patients under JAK inhibitor (JAKi) therapy.
AIM To study the effect of JAKi treatment on the reduction of IR in RA patients with active disease.
METHODS A retrospective study was carried out from April 1, 2017 to March 31, 2021 in a population of non-diabetic patients with active RA who were undergoing tofacitinib (TOF) therapy with 5 mg twice-daily immediate-release formulation.
RESULTS Fifty-six RA patients, aged 30 years to 75 years (mean ± SD: 52.3 ± 11.1) with disease activity score 28 values ranging from 4.54 to 7.37 (5.82 ± 0.74), were classified into high-IR (> 2.0) and low-IR (≤ 2.0) groups based on their baseline homeostatic model assessment (HOMA)-IR levels. They had no previous exposure to JAKi, and received TOF therapy for no less than 6 mo. In 30 patients who were naïve to biologics, after a 24-week therapeutic period, the high-IR group showed reduced HOMA-IR levels (3.331 ± 1.036 vs 2.292 ± 0.707, P < 0.001). In another 26 patients who were exposed to tumor necrosis factor-α or interleukin-6 blockers, the high-IR group, despite having achieved a decrease but with lower magnitude than in naïve patients, showed reduced HOMA-IR levels (2.924 ± 0.790 vs 2.545 ± 1.080, P = 0.018).
CONCLUSION In this retrospective study, reduced IR was achieved in non-diabetic active RA patients following 24 wk of TOF therapy.
Collapse
Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| |
Collapse
|
|
14
|
Li J, Chen Y, Liu Q, Tian Z, Zhang Y. Mechanistic and therapeutic links between rheumatoid arthritis and diabetes mellitus. Clin Exp Med 2022; 23:287-299. [DOI: 10.1007/s10238-022-00816-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 02/24/2022] [Indexed: 02/07/2023]
|
|
15
|
Zhang Q, Jin D, Mou X, Ye H. PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis. J Clin Lab Anal 2022; 36:e24267. [PMID: 35104386 PMCID: PMC8906019 DOI: 10.1002/jcla.24267] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 01/18/2022] [Accepted: 01/21/2022] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE Cell division cycle 42 (CDC42) regulates the polarization of M2 macrophage and maintains the T cell homeostasis, to participate in multiple autoimmune diseases, while its clinical involvement in ankylosing spondylitis (AS) remains unclear. Hence, the current study aimed to investigate the correlation of CDC42 with clinical characteristics and treatment outcome in AS patients receiving tumor necrosis factor (TNF) inhibitor therapy. METHODS Peripheral blood mononuclear cell (PBMC) CDC42 expression was detected at baseline, week (W) 4, W8, and W12 after TNF inhibitor treatment in 91 AS patients and in 50 HCs after enrollment. Furthermore, serum TNF-α, interferon-γ (IFN-γ), interleukin-10 (IL-10), and interleukin-17A (IL-17A) from AS patients were detected at baseline. RESULTS Blood CDC42 was lower in AS patients compared with HCs (p < 0.001). Additionally, blood CDC42 was negatively linked with CRP (r = -0.349, p = 0.001), BASDAI score (r = -0.243, p = 0.020), and ASDASCRP score (r = -0.238, p = 0.023) in AS patients; however, blood CDC42 was not correlated with other clinical characteristics. Besides, CDC42 was negatively correlated with TNF-α (r = -0.237, p = 0.024) and IL-17A (r = -0.339, p = 0.001) but not with IFN-γ (p = 0.083) or IL-10 (p = 0.280). Moreover, blood CDC42 was elevated after TNF inhibitor treatment (p < 0.001). Meanwhile, blood CDC42 was not varied at baseline and W4 between response patients and non-response patients, while it was higher at W8 (p = 0.019) and W12 (p = 0.002) in response patients than in non-response patients after treatment. CONCLUSION Blood CDC42 deficiency links with elevated pro-inflammatory cytokines, disease activity and unsatisfying response to TNF inhibitor in AS patients.
Collapse
Affiliation(s)
- Qian Zhang
- Department of RheumatologyTaizhou First People’s HospitalTaizhouChina
| | - Du Jin
- Department of RheumatologyTaizhou First People’s HospitalTaizhouChina
| | - Xiaoyue Mou
- Department of RheumatologyTaizhou First People’s HospitalTaizhouChina
| | - Hengli Ye
- Department of OrthopedicsHuangyan Hospital Of Traditional Chinese MedicineTaizhouChina
| |
Collapse
|
|
16
|
Shu J, Li N, Wei W, Zhang L. Detection of molecular signatures and pathways shared by Alzheimer's disease and type 2 diabetes. Gene 2022; 810:146070. [PMID: 34813915 DOI: 10.1016/j.gene.2021.146070] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 10/21/2021] [Accepted: 11/16/2021] [Indexed: 01/12/2023]
Abstract
Alzheimer's disease (AD) and type 2 diabetes (T2D) are common in the general elderly population, conferring heavy individual, social, and economic stresses on families and society. Accumulating evidence indicates T2D to be a risk factor for AD. However, the underlying mechanisms for this association are largely unknown. This study aimed to identify the shared molecular signatures between AD and T2D through integrated analysis of temporal cortex gene expression data. Gene Ontology (GO) and pathway enrichment analysis, protein over-representation analysis, protein-protein interaction, DEG-transcription factor interactions, DEG-microRNA interactions, protein-drug interactions, gene-disease association analysis, and protein subcellular localization analysis of the common DEGs were performed. We identified 16 common DEGs between the two datasets, which were mainly enriched in the biological processes of apoptosis, autophagy, inflammation, and hemostasis. We also identified five hub proteins encoded by the DEGs, five central regulatory transcription factors, and six microRNAs. Protein-drug interaction analysis showed C1QB to be associated with different drugs. Gene-disease association analysis revealed that hub genes, SFN and ITGB2, were actively engaged in other diseases. Collectively, these findings provide new insights into shared molecular mechanisms between AD and T2D and provide novel candidate targets for therapeutic intervention.
Collapse
Affiliation(s)
- Jun Shu
- Department of Neurology, Cognitive Disorders Center, Huadong Hospital, Fudan University, No. 221, West Yan An Road, Shanghai, China
| | - Nan Li
- Department of Neurology, Cognitive Disorders Center, Huadong Hospital, Fudan University, No. 221, West Yan An Road, Shanghai, China
| | - Wenshi Wei
- Department of Neurology, Cognitive Disorders Center, Huadong Hospital, Fudan University, No. 221, West Yan An Road, Shanghai, China.
| | - Li Zhang
- Department of Neurology, Cognitive Disorders Center, Huadong Hospital, Fudan University, No. 221, West Yan An Road, Shanghai, China.
| |
Collapse
|
|
17
|
Cantini F, Goletti D, Benucci M, Foti R, Damiani A, Niccoli L. Tailored first-line biologic and targeted synthetic disease modifying anti-rheumatic drugs therapy in patients with rheumatoid arthritis: 2021 updated ITABIO statements. Expert Opin Drug Saf 2021; 21:613-623. [PMID: 34937466 DOI: 10.1080/14740338.2022.2020247] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
INTRODUCTION In 2015, the Italian board for the TAilored BIOlogic therapy (ITABIO) proposed evidence-based decisional statements for first-line tailored biologic therapy in patients with rheumatoid arthritis (RA). Taking into account the new licensed drugs, the aim of the present review was to update the previous statements. AREAS COVERED A narrative review of the most recent evidence on the efficacy and safety of old and newly licensed drugs for the treatment of articular and extra-articular RA was performed. In addition, host-related variables potentially driving the therapy choice, such as the infection risk, the cardiovascular risk, the risk of deep vein thrombosis, thromboembolism, pregnancy, and obesity were analyzed. Consequently, several statements for personalized therapy were formulated, thus providing a decisional algorithm useful for proper personalized therapy of RA patients in clinical practice. EXPERT OPINION Several clinical variables related to specific drug and host characteristics may drive the choice toward anti-TNF and non-anti-TNF biologics, or anti-JAKs, thus allowing to personalize the therapy. Consequently, the right therapy for the right patient would ensure a successful therapeutic intervention.
Collapse
Affiliation(s)
| | - Delia Goletti
- Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via,Portuense 292, 00149 Rome, Italy
| | - Maurizio Benucci
- Rheumatology Unit, Hospital S. Giovanni di Dio, Azienda USL-Toscana Centro, Florence, Italy
| | - Rosario Foti
- Rheumatology Unit, Vittorio-Emanuele University Hospital of Catania, Catania, Italy
| | - Arianna Damiani
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | - Laura Niccoli
- Rheumatology Department, Hospital of Prato, Prato Italy
| |
Collapse
|