Azathioprine-induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases—A Prospective Study on Incidence and Severity

Teich, Niels; Mohl, W; Bokemeyer, Bernd; Bündgens, Burkhard; Büning, Jürgen; Miehlke, Stephan; Hüppe, D; Maaser, Christian; Klugmann, Tobias; Kruis, Wolfgang; Siegmund, Britta; Helwig, Ulf; Weismüller, Josef; Drabik, Attyla; Stallmach, Andreas

doi:10.1093/ecco-jcc/jjv188

Cited by 91 publications

(101 citation statements)

References 39 publications

(49 reference statements)

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“…Regarding the etiology, the most frequent etiologies were postoperative and idiopathic, whereas the frequencies of biliary pancreatitis and post-ERCP pancreatitis were similar (12.5%). In our series, the treatment of IBD in patients having idiopathic acute pancreatitis was also evaluated; none of those patients were treated with azathioprine [13] or mesalazine [14], which have been reported to be causes of acute pancreatitis in IBD patients (probably based on direct toxicity and allergic mechanisms) or in patients with Crohn's disease associated with the blood group B [15] . The results of our study were similar to those previously reported showing that 21% of cases were due to biliary lithiasis, whereas the results of our data regarding idiopathic acute pancreatitis were higher than those previously reported [16,17] .…”

Section: Discussionmentioning

confidence: 99%

Benign Exocrine Pancreatic Diseases in Inflammatory Bowel Diseases

Pezzilli

Pagano²

2017

Dig Dis

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Background: Data regarding the involvement of the pancreas during the course of inflammatory bowel disease (IBD) are scarce and conflicting. Aim: To assess the frequency of benign pancreatic diseases, that is, acute pancreatitis, chronic pancreatitis (CP), and autoimmune pancreatitis (AIP), in a population with IBD. Methods: A search for patients with IBD who presented at our hospital between January 2006 and January 2015 with a diagnosis of IBD was carried out. Patients: A total of 5,242 patients with IBD were included in this study (2,838 males, 54.1%, and 2,404 females, 45.9%, mean age 43.7 years, range 18-101 years). Of these 5,242 patients, 3,201 (61.1%) had Crohn's disease and 2,041 (38.9%) had ulcerative colitis (UC). Results: Thirteen patients developed benign pancreatic diseases (0.2%). Eight patients had acute pancreatitis (0.2%; 4 in the Crohn's disease group and 4 in the UC group), 3 had CP (0.1%, 2 in the Crohn's disease group and 1 in the UC group), 2 had AIP (0.04%), all in the group of diffuse UC (p = 0.321). Conclusions: The frequency of benign pancreatic disease was not high in patients with IBD and was probably similar to that seen in the general population.

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Section: Discussionmentioning

confidence: 99%

Benign Exocrine Pancreatic Diseases in Inflammatory Bowel Diseases

Pezzilli

Pagano²

2017

Dig Dis

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“…Typical adverse effects of some immunosuppressive substances such as azathioprine are an increased risk for infections and possibly a low risk for lymphoma and non-melanoma skin cancer in the long term [7, 13, 14]. Moreover, there are substance-specific side effects like azathioprine-induced acute pancreatitis [15] or infliximab-associated anaphylactic reactions [16]. …”

Section: Therapy In CD – Goals and Controlsmentioning

confidence: 99%

“…Typical side effects of thiopurines are, for example, fatigue, acute pancreatitis, increased susceptibility for infections and in the long-term potentially lymphoma and non-melanoma skin cancer [8, 32]. The strongest risk factor for azathioprine-induced acute pancreatitis is smoking [15]. Because of convincing data for biologicals, immunomodulators were less frequently used in recent years [32].…”

Section: Approved Substances – State Of the Artmentioning

confidence: 99%

Treatment Perspectives in Crohn’s Disease

Vetter¹

2018

Digestion

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Background: Crohn’s disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. The pathophysiological understanding of this disease is limited and no curative therapy is available so far. Therefore, most patients require long-lasting or even life-long immunosuppressive therapies for the suppression of symptoms to improve quality of life and reduction of long-term risks. However, in a relevant subgroup of patients, these therapeutic goals cannot be sufficiently attained. Summary: Clinically established therapies in active CD comprise corticosteroids and immunosuppressants such as azathioprine. After the introduction of anti-TNFα (Tumor necrosis factor alpha) antibodies, other biologicals (e.g., vedolizumab and ustekinumab) have also been approved. New drugs in the pipeline like filgotinib, upadacitinib, risankizumab or rifaximin could improve the therapy of CD in the near future. Thus, an individualized therapy management, based on optimal selection of therapeutic agents will become more important. Additionally, the local application of mesenchymal stem cells might be helpful in the management of fistulas. Key Messages: The targeted biological therapeutic agents (anti-TNFα antibodies, vedolizumab, ustekinumab) are well established for therapy in CD. There are several new substances in the pipeline with promising results in phase II trials (filgotinib, rifaximin, risankizumab, upadacitinib). The upcoming extension of the therapeutic arsenal will require methods for an optimized selection of substances, thus enabling a more individualized therapy.

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“…Можно предполо-жить, что повышенная активность фермента у носителей генотипа 3404AG может способство-вать усиленной генерации супероксидного ани-онного радикала, развитию окислительного стресса, повреждению митохондрий и таким об-разом способствовать запуску каскада деструк-тивных изменений в поджелудочной железе, вы-званных высвобождением пищеварительных ферментов. Подобный механизм развития острого панкреатита предполагается на фоне лечения аза-тиоприном [12]. В то же самое время ассоциация генотипа 3404AG с повышенным риском разви-тия ХП нами обнаружена только у женщин.…”

Section: результаты исследования и их обсуждениеunclassified

“…Тот факт, что фермент экспрессируется в достаточно большом количестве в клетках поджелудочной железы, свидетельствует о его потенциальной вовлеченности в важнейшие физиологические и патологические процессы в данном органе. При-мечательно, что один из субстратов АОХ1 являет-ся иммунодепрессант азатиоприн -лекарствен-ный препарат, способный провоцировать разви-тие острого панкреатита [3,12].…”

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Роль полиморфизма (rs55754655) гена фермента антиоксидантной системы в развитии хронического панкреатита

Самгина¹,

Канищев²,

Ханан³

et al. 2017

Курск. науч.-практ. вестн. «Человек и его здоровье»

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1 Кафедра хирургических болезней № 2, 2 кафедра биологии, медицинской генетики и экологии, 3 кафедра хирургических болезней ФПО Курского государственного медицинского университета, Курск E-mail: tass@list.ru Важная роль в развитии хронического панкреатита (ХП) отводится действию токсических веществ и нарушению регуляции процессов про-и антиоксидантной защиты. Одним из прооксидантных ферментов является альдегидокси-даза (АОХ1), которая играет ключевую роль в метаболизме ксенобиотиков. Цель исследования -изучение связи поли-морфизма (rs55754655) гена AOX1 с развитием ХП в русской популяции. Образцы цельной крови были собраны у 241 больного ХП и 132 здоровых индивидов. Генотипирование полиморфизма (rs55754655) гена AOX1 выполнено с по-мощью метода ПЦР с дискриминацией аллелей с помощью TaqMan-зондов. Обнаружено, что носительство аллеля G (OR=2.49 95% CI 1.27-4.88 p=0.01) и генотипа А/G ассоциировалось с повышенным риском развития ХП (OR=2.8 95% CI 1.32-5.86 p=0.01). Проведенный стратифицированный анализ по полу показал, что генотип А/G ассоциирован с раз-витием ХП только у женщин (OR=2.57 95% CI 1.09-6.04 p=0.01). Курящие пациенты с генотипом A/G имеют высокий риск развития ХП (OR =6.47 95%CI 0.82-51.23, р=0.05).Ключевые слова: хронический панкреатит, полиморфизм rs55754655 гена альдегидоксидазы. An important role in the development of chronic pancreatitis (CP) is given to the action of toxic substances and the disruption of the regulation of pro-and antioxidant defense processes. One of the prooxidant enzymes is aldehyde oxidase (AOX1), which plays a key role in the metabolism of xenobiotics. The aim of the study was to study the relationship between the polymorphism (rs55754655) of the AOX1 gene and the development of CP in the Russian population. Whole blood samples were collected from 241 patients with CP and 132 healthy individuals. Genotyping of the polymorphism (rs55754655) of the AOX1 gene was performed using the PCR method with discrimination of alleles with the help of TaqMan probes. It was found that the carriage of the G allele (OR = 2.49 95% CI 1.27-4.88 p = 0.01) and the A / G genotype was associated with an increased risk of developing CP (OR = 2.8 95% CI 1.32-5.86 p = 0.01). The stratified gender analysis showed that the genotype A / G was associated with the development of CP only in women (OR = 2.57 95% CI 1.09-6.04 p = 0.01). Smokers with A / G genotype have a high risk of developing chronic pancreatitis (OR = 6.47 95% CI 0.82-51.23, p = 0.05). ROLE OF THE POLYMORPHISM (rs55754655) OF THE ENZYME GENE OF THE ANTIOXIDANT SYSTEM IN THE DEVELOPMENT OF CHRONIC PANCREATITIS

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Azathioprine-induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases—A Prospective Study on Incidence and Severity

Cited by 91 publications

References 39 publications

Benign Exocrine Pancreatic Diseases in Inflammatory Bowel Diseases

Benign Exocrine Pancreatic Diseases in Inflammatory Bowel Diseases

Treatment Perspectives in Crohn’s Disease

Роль полиморфизма (rs55754655) гена фермента антиоксидантной системы в развитии хронического панкреатита

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