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Huang Y, Ru Q, Ruan H, Zhang J, Wang Y, Wang C, Chen C, Yu D, Luo J, Yang M. Changyanning tablet alleviates Crohn's disease by inhibiting GPX4-mediated ferroptosis. JOURNAL OF ETHNOPHARMACOLOGY 2025; 342:119415. [PMID: 39870334 DOI: 10.1016/j.jep.2025.119415] [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: 12/17/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 01/29/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Changyanning tablets (CYN) are a marketed traditional Chinese medicine composed of Diijincao (Euphorbia humifusa Willd.), Jinmaoercao (Hedyotis chrysotricha (Palib.) Merr.), Zhangshugen (root of Cinnamomum camphora (L.) J.Presl), Xiangru (Elsholtzia ciliate (Thunb.) Hyl.), and Fengxiangshuye (leaf of Liquidambar formosana Hance). They possess the functions of clearing heat, removing dampness, and regulating qi. CYN is used for the treatment of diarrhea and dysentery caused by damp heat in the large intestine, with symptoms such as diarrhea, or stools with pus and blood, tenesmus, abdominal pain and distension, acute and chronic gastroenteritis, diarrhea, bacterial diarrhea, and indigestion in children. AIM OF THE STUDY This study aims to explore the intervention effects of CYN on Crohn's disease (CD) and its potential mechanisms. MATERIALS AND METHODS The therapeutic effect and potential mechanism of CYN on CD were investigated based on the 2,4,6-Trinitrobenzenesulfonic acid solution (TNBS)-induced rat model. In vivo and in vitro experiments confirmed that CYN can alleviate CD by inhibiting GPX4-mediated ferroptosis. siRNA was used to knock down GPX4 for reverse validation. Finally, active components of CYN inhibiting ferroptosis were identified using UPLC-MS and the RSL3-induced HCoEpiC ferroptosis cell model. RESULTS CYN significantly improved ferroptosis-related indicators (GSH, MDA, GPX4, and SLC7A11) in the colons of TNBS-induced CD rats. Screening with three ferroptosis inducers (RSL3, FINO2, and erastin) revealed that CYN was most effective against RSL3 (a ferroptosis inducer targeting GPX4)-induced apoptosis. Subsequently, the resistance effect of CYN on RSL3-induced ferroptosis was confirmed in vitro. Further in vivo experiments showed that CYN alleviated local CD-like intestinal injury induced by RSL3 enema. siRNA knockdown of GPX4 in HCoEpiC cells further validated GPX4 as major target of CYN in inhibiting ferroptosis. Finally, UPLC-MS and in vitro experiments identified rutin, rosmarinic acid, and kaempferol-3-O-sophoroside as key active components of CYN for inhibiting ferroptosis. CONCLUSIONS CYN alleviates CD by inhibiting GPX4-mediated ferroptosis, highlighting its clinical potential for treating CD and enhancing the understanding of the pathogenic and therapeutic mechanisms associated with CD.
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Affiliation(s)
- Ying Huang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
| | - Qing Ru
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
| | - Haonan Ruan
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
| | - Jing Zhang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
| | - Yunyun Wang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
| | - Chuang Wang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
| | - Changyong Chen
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
| | - Defa Yu
- Jiangxi Kangenbei Traditional Chinese Medicine Co., Ltd., Shangrao, 334400, China.
| | - Jiaoyang Luo
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
| | - Meihua Yang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
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Bhardwaj A, Singh A, Midha V, Sood A, Wander GS, Mohan B, Batta A. Cardiovascular implications of inflammatory bowel disease: An updated review. World J Cardiol 2023; 15:553-570. [PMID: 38058397 PMCID: PMC10696203 DOI: 10.4330/wjc.v15.i11.553] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 10/22/2023] [Accepted: 11/08/2023] [Indexed: 11/23/2023] Open
Abstract
Emerging data highlights the heightened risk of atherosclerotic cardiovascular diseases (ASCVD) in patients with chronic inflammatory disorders, particularly those afflicted with inflammatory bowel disease (IBD). This review delves into the epidemiological connections between IBD and ASCVD, elucidating potential underlying mechanisms. Furthermore, it discusses the impact of current IBD treatments on cardiovascular risk. Additionally, the cardiovascular adverse effects of novel small molecule drugs used in moderate-to-severe IBD are investigated, drawing parallels with observations in patients with rheumatoid arthritis. This article aims to comprehensively evaluate the existing evidence supporting these associations. To achieve this, we conducted a meticulous search of PubMed, spanning from inception to August 2023, using a carefully selected set of keywords. The search encompassed topics related to IBD, such as Crohn's disease and ulcerative colitis, as well as ASCVD, including coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, conduction abnormalities, heart blocks, and premature coronary artery disease. This review encompasses various types of literature, including retrospective and prospective cohort studies, clinical trials, meta-analyses, and relevant guidelines, with the objective of providing a comprehensive overview of this critical intersection of inflammatory bowel disease and cardiovascular health.
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Affiliation(s)
- Arshia Bhardwaj
- Department of Gastroenterology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Gurpreet Singh Wander
- Department of Cardiology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Bishav Mohan
- Department of Cardiology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India
| | - Akash Batta
- Department of Cardiology, Dayanand Medical College and Hospital, Punjab, Ludhiana 141001, India.
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Chen J, Pan M, Wang J, Zhang M, Feng M, Chai X, Zhang Q, Sun Y. Hydroxysafflor yellow A protects against colitis in mice by suppressing pyroptosis via inhibiting HK1/NLRP3/GSDMD and modulating gut microbiota. Toxicol Appl Pharmacol 2023; 467:116494. [PMID: 37001609 DOI: 10.1016/j.taap.2023.116494] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 03/14/2023] [Accepted: 03/26/2023] [Indexed: 03/31/2023]
Abstract
Hydroxysafflor yellow A (HSYA), a chalcone glycoside, is a component of Carthamus tinctorius L. and exerts anti-inflammatory and antioxidative effects. However, the therapeutic effect and the underlying mechanism of HSYA on ulcerative colitis is unclear. This study aimed to investigate the unexplored protective effects and underlying mechanisms of HSYA on UC. In vitro analyses showed that HSYA reduced the secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 and inhibited nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD)-mediated pyroptosis in lipopolysaccharide/ adenosine-5'-triphosphate (LPS/ATP)-stimulated macrophages. Gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites showed that HSYA reduced the increased levels of glucose, glucose 6-phosphate, and lactic acid, and inhibited the increased hexokinase 1 (HK1) expression caused by LPS/ATP stimulation. HK1 shRNA transfection further confirmed that HSYA inhibited the NLRP3/GSDMD-mediated pyroptosis via HK1 downregulation. In vivo analyses showed that HSYA drastically attenuated UC symptoms by relieving body weight loss, a decline in colon length, and inflammatory infiltration in colonic tissues induced by dextran sulfate sodium (DSS). HSYA also reduced the secretion of pro-inflammatory cytokines including IL-1β, IL-6, TNF-α, and IL-18. Moreover, HSYA inhibited HK1/NLRP3/GSDMD-mediated pyroptosis in DSS-induced colitis mice. Finally, 16S rRNA sequencing analyses of gut microbiota revealed that HSYA reversed gut microbiota dysbiosis by reducing the abundance of Proteobacteria and increasing that of Bacteroidetes. This study demonstrated that HSYA not only exerted anti-inflammatory effects by inhibiting HK1/NLRP3/GSDMD and suppressing pyroptosis but also regulated gut microbiota in mice with DSS-induced colitis. Our findings provide new experimental evidence that HSYA might be a potential candidate for treating inflammatory bowel diseases.
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Affiliation(s)
- Jiaxi Chen
- School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China; College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China
| | - Mengyue Pan
- School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China
| | - Jingjie Wang
- School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China
| | - Mengling Zhang
- School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China
| | - Mingmei Feng
- School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China
| | - Xiaoming Chai
- School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China
| | - Qi Zhang
- School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China; College of Food Science and Light Industry, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China.
| | - Yang Sun
- School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China.
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Patel RS, Rohit Reddy S, Llukmani A, Hashim A, Haddad DR, Patel DS, Ahmad F, Gordon DK. Cardiovascular Manifestations in Inflammatory Bowel Disease: A Systematic Review of the Pathogenesis and Management of Pericarditis. Cureus 2021; 13:e14010. [PMID: 33884251 PMCID: PMC8054944 DOI: 10.7759/cureus.14010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition of the bowel that can be further categorized into ulcerative colitis and Crohn’s disease. Rarely, this condition can be associated with pericarditis, which can be an extraintestinal manifestation of the disease or drug-induced. This review aims to determine the pathogenesis and management of pericarditis in IBD. In this review, the goal is to elucidate the pathogenesis of pericarditis in IBD and determine if pericarditis is an extraintestinal manifestation of IBD or a complication of current drug therapy used to manage IBD. Additionally, this review intends to explain the first-line management of pericarditis in IBD and explore the role of biologicals in attenuating pericarditis. An electronic search was conducted to identify relevant reports of pericarditis in IBD, and a quality assessment was conducted to identify high-quality articles according to the inclusion criteria. Full-text articles from inception to November 2020 were included, while non-English articles, gray literature, and animal studies were excluded. The majority of studies suggest that pericarditis arises as a complication of drug therapy by 5-aminosalicylic acid derivatives such as sulfasalazine, mesalamine, and balsalazide, and it occurs due to IgE-mediated allergic reactions, direct cardiac toxicity, cell-mediated hypersensitivity reactions, and humoral antibody response to therapy. Drug cessation or the initiation of a corticosteroid regimen seems to be the most effective means of managing pericarditis in IBD due to drug therapy or an extraintestinal manifestation.
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Affiliation(s)
- Ravi S Patel
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Sai Rohit Reddy
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Adiona Llukmani
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ayat Hashim
- Behavioral Neurosciences and Psychology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Dana R Haddad
- Plastic and Reconstructive Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Dutt S Patel
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Farrukh Ahmad
- Emergency Department, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Domonick K Gordon
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Taha ME, Abdalla A, Al-Khafaji J, Malik S. Mesalamine-Induced Myopericarditis: A Case Report and Literature Review. Cardiol Res 2019; 10:59-62. [PMID: 30834061 PMCID: PMC6396800 DOI: 10.14740/cr820] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Accepted: 12/27/2018] [Indexed: 01/05/2023] Open
Abstract
Inflammation of the myocardium (myocarditis) or pericardium (pericarditis) or both (myopericarditis) as side effects of mesalamine, a drug widely used in the treatment of inflammatory bowel disease, is a rare, but potentially lethal complication. We report a case of myopericarditis occurring in a young Caucasian woman 14 days following initiation of mesalamine therapy for treatment of a newly diagnosed ulcerative colitis (UC). She presented with pleuritic chest pain, elevated troponin levels and pre-syncope. The diagnosis of myopericarditis was made based on the clinical features, electrocardiogram (EKG) and cardiac magnetic resonance, which showed trace pericardial effusion. The patient’s symptom and condition were dramatically improved upon discontinuing mesalamine, and a full recovery was achieved. Mesalamine-induced inflammation of the myocardium (myocarditis) or pericardium (pericarditis) or both (myopericarditis) is rare, but has fatal side effects. Early recognition of these side effects by clinicians and patients is important to prevent progression of the inflammation. Furthermore, patients should be educated to seek urgent medical attention if cardiac symptoms arise.
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Affiliation(s)
- Mohamed E Taha
- Department of Internal Medicine, University of Nevada - Reno, School of Medicine, Reno, NV 89502, USA
| | - Abubaker Abdalla
- Department of Internal Medicine, University of Nevada - Reno, School of Medicine, Reno, NV 89502, USA
| | - Jaafar Al-Khafaji
- Department of Internal Medicine, University of Nevada - Reno, School of Medicine, Reno, NV 89502, USA
| | - Samira Malik
- Department of Internal Medicine, University of Nevada - Reno, School of Medicine, Reno, NV 89502, USA
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Pizarro Carbajo I, Gutiérrez Macías A, Cea Gómez M, Lombide Aguirre I. Fever induced by mesalazine. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:261-262. [PMID: 28431755 DOI: 10.1016/j.gastrohep.2017.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Revised: 03/13/2017] [Accepted: 03/17/2017] [Indexed: 06/07/2023]
Affiliation(s)
- Izaskun Pizarro Carbajo
- Unidad de Medicina Familiar y Comunitaria, OSI Bilbao-Basurto, Hospital Universitario Basurto, Bilbao, Vizcaya, España
| | - Alfonso Gutiérrez Macías
- Servicio de Medicina Interna, OSI Bilbao-Basurto, Hospital Universitario Basurto, Bilbao, Vizcaya, España.
| | - Markel Cea Gómez
- Unidad de Medicina Familiar y Comunitaria, OSI Bilbao-Basurto, Hospital Universitario Basurto, Bilbao, Vizcaya, España
| | - Itxaso Lombide Aguirre
- Servicio de Medicina Interna, OSI Bilbao-Basurto, Hospital Universitario Basurto, Bilbao, Vizcaya, España
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McClelland TJ, Penfold R, Kluzek S, Nagra NS. A large chronic pericardial effusion in an ultramarathon runner with anti-CCP positive rheumatoid arthritis. BMJ Case Rep 2017; 2017:bcr-2017-219350. [PMID: 28611162 DOI: 10.1136/bcr-2017-219350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Pericardial effusions arise as an extra-articular manifestation of rheumatoid arthritis (RA). Pericardial effusions are often asymptomatic, particularly in the early phase, but patients are at risk of cardiac tamponade as the effusion progresses. We discuss the case of a 40-year-old male ultramarathon runner with RA who presented with mild pleuritic chest pain and exertional dyspnoea after a recent long-haul flight. Despite a relative tachycardia, his observations were otherwise unremarkable. His blood tests revealed a C-reactive protein (CRP) of 86 mg/L and an anti-cyclic citrullinated peptide (anti-CCP) titre of 360 units/mL. He was initially diagnosed with a pulmonary embolism; however, a large pericardial effusion was found incidentally on CT pulmonary angiogram with over 1500 mL subsequently drained. The patient's symptoms resolved and CRP normalised 2 weeks later. This unique case illustrates that physically fit patients may physiologically compensate for large pericardial effusions and that arthritic symptoms do not correlate with the severity of extra-articular features in RA.
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Affiliation(s)
| | - Rose Penfold
- Botnar Research Centre (NDORMS), University of Oxford, Oxford, UK
| | - Stefan Kluzek
- Botnar Research Centre (NDORMS), University of Oxford, Oxford, UK
| | - Navraj S Nagra
- Botnar Research Centre (NDORMS), University of Oxford, Oxford, UK
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Brown G. 5-Aminosalicylic Acid-Associated Myocarditis and Pericarditis: A Narrative Review. Can J Hosp Pharm 2016; 69:466-472. [PMID: 28123193 PMCID: PMC5242279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
BACKGROUND Use of medications containing the 5-aminosalicylic acid (5-ASA) moiety may cause a rare but potentially lethal side effect involving inflammation of the heart (myocarditis) or pericardium (pericarditis) or both (myopericarditis). Early recognition of 5-ASA as the cause is important to prevent progression of the inflammation. OBJECTIVE To provide clinicians with information to assist in recognizing the signs and symptoms of 5-ASA-induced cardiac inflammation and the characteristics of the suspected therapy, and in determining the appropriate approach to treatment. DATA SOURCES STUDY SELECTION AND DATA EXTRACTION The Embase database was searched, for the period 1974 to July 17, 2015, for published descriptions of cases of cardiac inflammation caused by 5-ASA-containing medications. The search terms included the names of specific agents, as well as terms for different types of cardiac inflammation. Articles in any language were retained for inclusion in this narrative review. FINDINGS There is no symptom, sign, laboratory test, or constellation of symptoms and signs that is pathognomonic for 5-ASA-induced myocardial-pericardial toxicity. Similarly, there is no single laboratory, electrocardiographic, or echocardiographic finding or combination of findings that implicates 5-ASA as the cause of nonspecific symptoms. However, most patients present with chest pain, shortness of breath, and fever within the first 28 days after initiating 5-ASA. Physical examination, electrocardiography, and diagnostic imaging will yield findings consistent with myocarditis, with or without accompanying pericarditis. Prompt discontinuation of the 5-ASA will result in resolution of symptoms within days, without the need for any adjunctive therapies. Rechallenge with any 5-ASA-containing compound carries a high risk for recurrence of the inflammation. CONCLUSIONS Any patient presenting with chest pain, shortness of breath, or fever within 28 days after initiating a 5-ASA-containing drug should be considered as exhibiting drug-induced inflammation. The 5-ASA-containing drug should be stopped immediately until other causes can be proven (or excluded); if no other cause is discovered, the 5-ASA should not be restarted.
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Affiliation(s)
- Glen Brown
- Address correspondence to: Dr Glen Brown, Pharmacy, St Paul’s Hospital, 1081 Burrard Street, Vancouver BC V6Z 1Y6, e-mail:
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Izzo R, Bevivino G, Monteleone G. Tofacitinib for the treatment of ulcerative colitis. Expert Opin Investig Drugs 2016; 25:991-7. [PMID: 27177233 DOI: 10.1080/13543784.2016.1189900] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Management of patients with active ulcerative colitis (UC), one of the most frequent inflammatory bowel diseases in human beings, is mainly based on the use of mesalamine and corticosteroids. Since in the long-term, these two drugs may be ineffective in nearly one third of the patients, immunosuppressants and/or biologics are needed to control disease activity. AREAS COVERED The marked activation of JAK/STAT molecules in inflamed mucosa of UC patients and the demonstration that UC-associated mucosal injury is driven by soluble factors that signal through JAK/STAT pathways led to investigation of JAK inhibitors for the treatment of active UC. Tofacitinib, an oral inhibitor of the cytokine-driven JAK-STAT signalling cascade, has recently been proposed for the treatment of moderate-to-severe UC. Phase 2 study showed the efficacy of tofacitinib to induce clinical and endoscopic improvement/remission and the safety profile of the drug. Herein the authors review this compound. EXPERT OPINION The results obtained from clinical trials with tofacitinib suggest that this drug could be a new treatment option for patients with moderate to severe UC. However, further experimentation is needed to assess the efficacy of this drug in selected subgroups of patients as well as to maintain remission and to determine the long-term safety profile of the drug.
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Affiliation(s)
- Roberta Izzo
- a Department of Systems Medicine , University of Rome 'Tor Vergata' , Rome , Italy
| | - Gerolamo Bevivino
- a Department of Systems Medicine , University of Rome 'Tor Vergata' , Rome , Italy
| | - Giovanni Monteleone
- a Department of Systems Medicine , University of Rome 'Tor Vergata' , Rome , Italy
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Neto R, Ferdinande L, Hindryckx P, Liesbeth F, Hindryckx P, Pieter H. Not a Usual Flare up of Ulcerative Colitis. Gastroenterology 2015; 148:1284-7. [PMID: 25936952 DOI: 10.1053/j.gastro.2014.12.053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Accepted: 12/29/2014] [Indexed: 12/02/2022]
Affiliation(s)
| | | | - Pieter Hindryckx
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | | | - Pieter Hindryckx
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
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Ding H, Liu XC, Mei Q, Xu JM, Hu XY, Hu J. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity. World J Gastroenterol 2014; 20:3716-3718. [PMID: 24707159 PMCID: PMC3974543 DOI: 10.3748/wjg.v20.i13.3716] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2013] [Revised: 11/05/2013] [Accepted: 12/12/2013] [Indexed: 02/06/2023] Open
Abstract
Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.
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Coman RM, Glover SC, Gjymishka A. Febrile pleuropericarditis, a potentially life-threatening adverse event of balsalazide – case report and literature review of the side effects of 5-aminosalicylates. Expert Rev Clin Immunol 2014; 10:667-75. [DOI: 10.1586/1744666x.2014.902313] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Awano N, Ryu T, Yoshimura N, Takazoe M, Kitamura S, Tanaka M. Successful treatment of ulcerative colitis associated with hypereosinophilic syndrome/chronic eosinophilic leukemia. Intern Med 2011; 50:1741-5. [PMID: 21841337 DOI: 10.2169/internalmedicine.50.5569] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 23-year-old female was diagnosed as having simultaneous ulcerative colitis (UC) relapse and hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL) without FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) fusion gene. Pathological findings of colon specimens were compatible with UC, however, focal severe infiltration of eosinophils was observed in the rectum, which is unusual in UC, suggesting eosinophil-mediated organ damage. Although imatinib mesylate (IM) is usually ineffective for the treatment of HES/CEL with negative-F/P fusion gene, in the present case it led to the remission of HES/CEL and UC at a higher drug dosage level (400 mg/day). That suggested the presence of unknown tyrosine kinase abnormalities not yet categorized.
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Affiliation(s)
- Nobuyasu Awano
- Department of Internal Medicine, Social Insurance Chuo General Hospital, Japan
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