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https://www.readbyqxmd.com/read/28095714/disease-related-and-drug-induced-skin-manifestations-in-inflammatory-bowel-disease
#1
Pieter Hindryckx, Gregor Novak, Antonio Costanzo, Silvio Danese
Skin manifestations are common in patients with inflammatory bowel diseases (IBD) and can be part of a concomitant illness with a shared genetic background, an extra-intestinal manifestation of the disease, or a drug side-effect. Areas covered: We provide a practical overview of the epidemiology, pathogenesis, diagnosis, therapeutic approach and prognosis of the most frequent disease-related and drug-induced cutaneous manifestations in IBD, illustrated by cases encountered in our clinical practice. Among the most frequently encountered IBD-related lesions are erythema nodosum, pyoderma gangrenosum and Sweet's syndrome...
January 17, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28095263/chemoprevention-of-colorectal-cancer-in-inflammatory-bowel-disease
#2
Adam C Ehrlich, Shyam Patel, Andrew Mellier, Robin D Rothstein, Frank K Friedenberg
Patients with inflammatory bowel disease are at an increased risk of colorectal cancer when compared to the general population. Chronic inflammation is thought to be the underlying cause, and medications that reduce inflammation have the potential to reduce the risk of colorectal cancer. Areas covered: After conducting a PubMed search for relevant literature, we examined several classes of medications that have been studied as potential chemopreventive agents. These include 5-aminosalicylates, thiopurines, tumor necrosis factor antagonists, ursodeoxycholic acid, NSAIDs, and statins...
January 17, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28088792/impact-of-nudt15-polymorphisms-on-thiopurines-induced-myelotoxicity-and-thiopurines-tolerance-dose
#3
Dandan Yin, Xuyang Xia, Junlong Zhang, Shouyue Zhang, Fei Liao, Ge Zhang, Yan Zhang, Qianqian Hou, Xue Yang, Hong Wang, Zhigui Ma, Heyao Wang, Yiping Zhu, Wei Zhang, Yuelan Wang, Bo Liu, Lanlan Wang, Heng Xu, Yang Shu
Thiopurines are widely used as anticancer and immunosuppressive agents. However, life-threatening myelotoxicity has been noticed and largely explained by genetic variations, including NUDT15 polymorphisms (e.g., rs116855232). In this study, we conduct a meta-analysis to investigate the impact of rs116855232 on thiopurines-induced myelotoxicity susceptibility (1752 patients from 7 independent cohorts), as well as on thiopurines intolerance dose (2745 patients from 13 cohorts). Variant allele of rs116855232 contributes 7...
January 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28081040/azathioprine-therapy-in-a-pediatric-tpmt-deficient-patient-still-an-option
#4
S A W van Moorsel, N Bevers, M Meurs, L K van Rossum, P M Hooymans, D R Wong
We describe the case of a pediatric patient on azathioprine therapy with previously undiagnosed homozygote thiopurine S-methyltransferase (TPMT) deficiency, resulting in myelotoxic thiopurine metabolite levels. The patient was successfully treated with a very low azathioprine dose of 50 mg once a week (4% of standard dose), guided by frequent thiopurine metabolite measurement and a close clinical surveillance. We demonstrate that azathioprine therapy still might be an effective and safe therapeutic option in pediatric thiopurine S-methyltransferase-deficient IBD patients...
February 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28078646/mucosal-healing-in-ulcerative-colitis-a-comprehensive-review
#5
REVIEW
Pedro Boal Carvalho, José Cotter
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28060115/hepatotoxicity-during-maintenance-therapy-and-prognosis-in-children-with-acute-lymphoblastic-leukemia
#6
Maria S Ebbesen, Ulrikka Nygaard, Susanne Rosthøj, Ditte Sørensen, Jacob Nersting, Kim Vettenranta, Finn Wesenberg, Jon Kristinsson, Arja Harila-Saari, Kjeld Schmiegelow
Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine aminotransferases (ALAT) levels and relapse rate. We included 385 patients enrolled in the NOPHO ALL-92 protocol. Data on ALAT levels, 6 MP and MTX doses, cytotoxic MTX/6 MP metabolites, and thiopurine methyltransferase (TPMT) activity were prospectively registered...
January 5, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28058028/hepatosplenic-t-cell-lymphoma-in-a-47-year-old-crohn-s-disease-patient-on-thiopurine-monotherapy
#7
Maartje M van de Meeberg, Lauranne A A P Derikx, Harm A M Sinnige, Peet Nooijen, D Lucette Schipper, Loes H C Nissen
Hepatosplenic T-cell lymphoma (HSTCL) is a rare non-Hodgkin lymphoma with a high mortality rate. Higher incidence is reported in patients with inflammatory bowel disease, specifically in male patients that are younger than 35 years, and have been treated with thiopurine and tumor necrosis factor (TNF)-α inhibitor combination therapy for over 2 years. In this case report we describe a 47-year-old patient with Crohn's disease (CD) who developed HSTCL after having been treated with thiopurine monotherapy for 14 years...
December 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28045204/increased-non-melanoma-skin-cancer-risk-in-young-patients-with-inflammatory-bowel-disease-on-immunomodulatory-therapy-a-retrospective-single-centre-cohort-study
#8
J Clowry, J Sheridan, R Healy, S Deady, D Keegan, K Byrne, G Cullen, H Mulcahy, H Comber, A C Parnell, G Doherty, A Lally
BACKGROUND: Recent studies report an increased risk of non-melanoma skin cancer (NMSC) in immunosuppressed patients with inflammatory bowel disease (IBD). Concurrently, paediatric IBD incidence is rising, with more patients now exposed to immunomodulators from a younger age. OBJECTIVES: To investigate NMSC incidence and to examine the risk associated with immunomodulators in the development of NMSC in patients with IBD. METHODS: This was a retrospective single centre cohort study...
January 3, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28028358/thiopurines-and-inflammatory-bowel-disease-current-evidence-and-a-historical-perspective
#9
REVIEW
Jordan E Axelrad, Abhik Roy, Garrett Lawlor, Burton Korelitz, Simon Lichtiger
The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn's disease...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28025747/enduring-value-of-thiopurines-for-inflammatory-bowel-disease-therapy
#10
EDITORIAL
Burton I Korelitz
No abstract text is available yet for this article.
December 26, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28011186/nk-cells-are-biologic-and-biochemical-targets-of-6-mercaptopurine-in-crohn-s-disease-patients
#11
Susy Yusung, Dermot McGovern, Lin Lin, Daniel Hommes, Venu Lagishetty, Jonathan Braun
NK cells, which contribute to immune defense against certain viral infections and neoplasia, are emerging as modifiers of chronic immunologic diseases including transplant rejection and autoimmune diseases. Immunobiology and genetic studies have implicated NK cells as a modifier of Crohn's disease, a condition often treated with thiopurine agents such as 6-mercaptopurine (6-MP). Here, we demonstrate that thiopurines mediate NK cell apoptosis via a caspase 3 and 9 inclusive pathway, and that this process is triggered by thiopurine-mediated inhibition of Rac1...
December 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28004405/expert-clinical-management-of-autoimmune-hepatitis-in-the-real-world
#12
R Liberal, Y S de Boer, R J Andrade, G Bouma, G N Dalekos, A Floreani, D Gleeson, G M Hirschfield, P Invernizzi, M Lenzi, A W Lohse, G Macedo, P Milkiewicz, B Terziroli, B van Hoek, J M Vierling, M A Heneghan
BACKGROUND: High-quality data on the management of autoimmune hepatitis (AIH) are scarce. Despite published guidelines, management of AIH is still expert based rather than evidence based. AIM: To survey expert hepatologists, asking each to describe their practices in the management of patients with AIH. METHODS: A survey questionnaire was distributed to members of the International AIH Group. The questionnaire consisted of four clinical scenarios on different presentations of AIH...
December 22, 2016: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27995656/the-effects-of-aminosalicylates-or-thiopurines-on-the-risk-of-colorectal-cancer-in-inflammatory-bowel-disease
#13
F Carrat, P Seksik, J-F Colombel, L Peyrin-Biroulet, L Beaugerie
BACKGROUND: Whether aminosalicylates or thiopurines reduce the risk of colorectal cancer (CRC) in inflammatory bowel (IBD) disease is controversial. AIM: To assess simultaneously the chemopreventive effect of aminosalicylates or thiopurines in a case-control study nested in the CESAME observational cohort that enrolled consecutive patients with IBD between May 2004 and June 2005. Patients were followed up to December 2007. METHODS: Study population comprised 144 case patients who developed CRC from the diagnosis of IBD (65 and 79 cases diagnosed, respectively, before and from 2004, starting year of the prospective observational period of CESAME) and 286 controls matched for gender, age, IBD subtype and year of diagnosis, and cumulative extent of colitis...
December 19, 2016: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27943397/early-prediction-of-thiopurine-induced-hepatotoxicity-in-inflammatory-bowel-disease
#14
D R Wong, M J H Coenen, L J J Derijks, S H Vermeulen, C J van Marrewijk, O H Klungel, H Scheffer, B Franke, H-J Guchelaar, D J de Jong, L G J B Engels, A L M Verbeek, P M Hooymans
BACKGROUND: Hepatotoxicity, gastrointestinal complaints and general malaise are common limiting adverse reactions of azathioprine and mercaptopurine in IBD patients, often related to high steady-state 6-methylmercaptopurine ribonucleotide (6-MMPR) metabolite concentrations. AIM: To determine the predictive value of 6-MMPR concentrations 1 week after treatment initiation (T1) for the development of these adverse reactions, especially hepatotoxicity, during the first 20 weeks of treatment...
February 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27941536/lc-ms-ms-analysis-of-erythrocyte-thiopurine-nucleotides-and-their-association-with-genetic-variants-in-patients-with-neuromyelitis-optica-spectrum-disorders-taking-azathioprine
#15
Shenghui Mei, Xindi Li, Xiaoqing Gong, Xingang Li, Li Yang, Heng Zhou, Yonghong Liu, Anna Zhou, Leting Zhu, Xinghu Zhang, Zhigang Zhao
BACKGROUND: Azathioprine (AZA) is a first-line drug in treating neuromyelitis optica spectrum disorders (NMOSD). To exhibit its bioactivity, AZA needs to be converted to thiopurine nucleotides (TPNs) including 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) that are affected by genetic polymorphisms. This study aims to develop an LC-MS/MS method for the analysis of erythrocyte concentrations of TPNs and to evaluate their associations with variants of various genes (MTHFR, TPMT, HLA, SLC29A1, SLC28A2, SLC28A3, ABCB1 and ABCC4) in patients with NMOSD...
November 29, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27875356/corticosteroids-and-thiopurines-but-not-tumor-necrosis-factor-antagonists-are-associated-with-cytomegalovirus-reactivation-in-inflammatory-bowel-disease-a-systematic-review-and-meta-analysis
#16
Tushar Shukla, Siddharth Singh, Parul Tandon, Jeffrey D McCurdy
BACKGROUND: The association between cytomegalovirus (CMV) reactivation and individual immunosuppressive agents in inflammatory bowel disease (IBD) has not been clearly defined. Therefore, we performed a systematic review and meta-analysis to assess this association. METHODS: Multiple electronic databases were searched systematically through July 2015 for observational studies reporting CMV reactivation (based on serum-based or tissue-based tests) in IBD patients stratified by medication exposure...
November 21, 2016: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/27867685/how-i-treat-my-inflammatory-bowel-disease-patients-with-thiopurines
#17
REVIEW
Berrie Meijer, Chris Jj Mulder, Adriaan A van Bodegraven, Nanne K H de Boer
Thiopurines are essential drugs to maintain remission in patients with inflammatory bowel disease (IBD). Thiopurines used in IBD are azathioprine (2.0-2.5 mg/kg), mercaptopurine (1.0-1.5 mg/kg) and thioguanine (0.2-0.3 mg/kg). However, mainly due to numerous adverse events associated with thiopurine use, almost 50% of the patients have to discontinue conventional thiopurine treatment. Extensive monitoring and the application of several treatment strategies, such as split-dose administration, co-administration with allopurinol or dose reduction/increase, may increase the chance of successful therapy...
November 6, 2016: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27862102/addition-of-an-immunomodulator-can-reverse-antibody-formation-and-loss-of-response-in-patients-treated-with-adalimumab
#18
B Ungar, U Kopylov, T Engel, M Yavzori, E Fudim, O Picard, A Lang, N Williet, S Paul, Y Chowers, A Bar-Gil Shitrit, R Eliakim, S Ben-Horin, X Roblin
BACKGROUND: Anti-adalimumab antibodies (AAA) are associated with loss of clinical response (LOR). Addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy. Similar data on adalimumab are lacking. AIM: To study the impact of immunomodulator addition on the emergence of AAA and LOR among adalimumab therapy patients. METHODS: The databases of three tertiary medical centres were reviewed to identify patients who developed AAA during adalimumab monotherapy with resultant LOR, and received an immunomodulator as a salvage combination therapy...
January 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27859568/6-methylmercaptopurine-induced-leukocytopenia-during-thiopurine-therapy-in-ibd-patients
#19
Berrie Meijer, Joany E Kreijne, Sofia A W van Moorsel, Luc J J Derijks, Gerd Bouma, Chris J J Mulder, Dennis R Wong, C Janneke van der Woude, Adriaan A van Bodegraven, Nanne K H de Boer
BACKGROUND: Thiopurines have a favorable benefit-risk ratio in the treatment of inflammatory bowel disease (IBD). A feared adverse event of thiopurine therapy is myelotoxicity, mostly occurring due to toxic concentrations of the pharmacologically active metabolites 6-thioguaninenucleotides. In oncology, myelosuppression has also been associated with elevated 6-methylmercaptopurine (6-MMP). In this case-series, we provide a detailed overview of 6-MMP-induced myelotoxicity in IBD patients...
November 16, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27853898/rate-and-predictors-of-mucosal-healing-in-ulcerative-colitis-treated-with-thiopurines-results-of-a-multicentric-cohort-study
#20
Caroline Prieux-Klotz, Stéphane Nahon, Aurelien Amiot, Leila Sinayoko, Carole Galéano-Cassaz, Stanislas Chaussade, Romain Coriat, Pierre Lahmek, Vered Abitbol
BACKGROUND AND AIMS: Mucosal healing (MH) with thiopurines has been poorly investigated in ulcerative colitis (UC). We aimed to assess MH rate in UC patients treated with thiopurine monotherapy. PATIENTS AND METHODS: We retrospectively collected all UC patients treated with thiopurines more than 6 months who have undergone colonoscopy at baseline and after at least 6 months of treatment. Patients were recruited from January 2005 to May 2015 through a personal database and/or standardized hospital inpatient diagnostic dataset...
November 16, 2016: Digestive Diseases and Sciences
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