Intestinal Research

Original Articles

Tuberculosis risk in patients with Crohn’s disease on biologics: a retrospective analysis of the Japanese Medical Claims Database: Koji Fujimoto, Shuhei Hosomi, Yumie Kobayashi, Rieko Nakata, Yu Nishida, Masaki Ominami, Yuji Nadatani, Shusei Fukunaga, Koji Otani, Fumio Tanaka, Satoko Ohfuji, Yasuhiro Fujiwara; Received May 27, 2024 Accepted July 17, 2024 Published online August 19, 2024; DOI: https://doi.org/10.5217/ir.2024.00076 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Treatment using tumor necrosis factor-α (TNF-α) inhibitors is one of the risk factors for active tuberculosis (TB) in patients with Crohn’s disease (CD). Biologics, such as ustekinumab (UST) and vedolizumab (VDZ), are less likely to cause opportunistic infections. However, large-scale studies for active TB and biologics other than TNF-α inhibitors are limited. We aimed to investigate the association between biologics and active TB utilizing a Japanese medical claims database.
Methods
We analyzed retrospectively the association of the risk of active TB development with treatment using TNF-α inhibitors and other biologics (UST and VDZ) in patients with CD using the Japanese Medical Data Vision (MDV) database between April 2008 and June 2022. The durations of each biologic and biologic-free treatment were calculated for each patient. Univariate and multivariate analyses were performed using the Cox proportional hazards model, with the utilization of biologics considered as time-dependent covariates.
Results
We included 28,811 patients with CD in MDV database. Finally, 17,169 patients were analyzed. In total, 7,064 patients were categorized as biologic-naïve, while 10,105 were classified as biologic-experienced. Seventeen patients developed active TB, including 7 on infliximab, 5 on adalimumab, and 5 on no biologics. None of the patients treated with UST and VDZ developed active TB. Multivariate analysis suggested that TNF-α inhibitors were the risk factors for active TB (hazard ratio, 3.66; P= 0.020).
Conclusions
TNF-α inhibitors, but not UST or VDZ, are risk factors for active TB in Japanese patients with CD.

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IBD

Infectious complications in patients with inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 8th Asian Organization for Crohn’s and Colitis meeting: Yu Kyung Jun, Seong-Joon Koh, Dae Seong Myung, Sang Hyoung Park, Choon Jin Ooi, Ajit Sood, Jong Pil Im; Intest Res 2023;21(3):353-362. Published online July 27, 2023; DOI: https://doi.org/10.5217/ir.2023.00013

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Infectious complications are major concerns when treating patients with inflammatory bowel disease (IBD). This study evaluated clinical differences across countries/regions in the management of infectious diseases in patients with IBD.
Methods
A multinational online questionnaire survey was administered to participants at the 8th meeting of the Asian Organization for Crohn’s and Colitis. The questionnaire included questions regarding surveillance, diagnosis, management, and prevention of infection in patients with IBD.
Results
A total of 384 physicians responded to the questionnaire. The majority of Korean (n=70, 63.6%) and Chinese (n=51, 51.5%) physicians preferred vancomycin to metronidazole in the treatment of Clostridium difficile infection, whereas more than half of the Japanese physicians (n=62, 66.7%) preferred metronidazole. Physicians in Korea (n=88, 80.0%) and China (n=46, 46.5%) preferred a 3-month course of isoniazid and rifampin to treat latent tuberculosis infection, whereas most physicians in Japan (n=71, 76.3%) favored a 9-month course of isoniazid. Most Korean physicians (n=89, 80.9%) recommended hepatitis B virus (HBV) vaccination in patients lacking HBV surface antigen, whereas more than half of Japanese physicians (n=53, 57.0%) did not consider vaccination.
Conclusions
Differences in the diagnosis, prevention, and management of infections in patients with IBD across countries/regions reflect different prevalence rates of infectious diseases. This survey may broaden understanding of the real-world clinical settings across Asian countries/regions and provide information for establishing practical guidelines to manage patients with IBD.

Citations

Citations to this article as recorded by

Characteristics and outcomes of portal vein thrombosis in patients with inflammatory bowel disease in Korea
Ki Jin Kim, Su-Bin Song, Jung-Bin Park, June Hwa Bae, Ji Eun Baek, Ga Hee Kim, Min-Jun Kim, Seung Wook Hong, Sung Wook Hwang, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Chang Sik Yu, Yong-Sik Yoon, Jong-Lyul Lee, Min Hy
The Korean Journal of Internal Medicine.2025; 40(2): 243. CrossRef
The Burden ofClostridioides difficileInfection in Korea
Seong Ran Jeon
Journal of Korean Medical Science.2024;[Epub] CrossRef
Perception of fecal microbiota transplantation in patients with ulcerative colitis in Korea: a KASID multicenter study
Jebyung Park, Sung Noh Hong, Hong Sub Lee, Jongbeom Shin, Eun Hye Oh, Kwangwoo Nam, Gyeol Seong, Hyun Gun Kim, Jin-Oh Kim, Seong Ran Jeon
The Korean Journal of Internal Medicine.2024; 39(5): 783. CrossRef
Assessing the associations of inflammatory bowel disease and hepatitis B virus infections with two-sample bidirectional mendelian randomization
Ping Han, Chaohui Wang, Yan Qiu
Critical Public Health.2024; 34(1): 1. CrossRef
Diagnosis, management, and prevention of infectious complications in inflammatory bowel disease: variations among Asian countries
Ji Eun Baek, Sung Wook Hwang
Intestinal Research.2023; 21(3): 277. CrossRef

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Infection

Interferon-gamma release assay has poor diagnostic accuracy in differentiating intestinal tuberculosis from Crohn’s disease in tuberculosis endemic areas: Karan Sachdeva, Peeyush Kumar, Bhaskar Kante, Sudheer K. Vuyyuru, Srikant Mohta, Mukesh K. Ranjan, Mukesh K. Singh, Mahak Verma, Govind Makharia, Saurabh Kedia, Vineet Ahuja; Intest Res 2023;21(2):226-234. Published online June 13, 2022; DOI: https://doi.org/10.5217/ir.2022.00010

Abstract PDF PubReader ePub

Background/Aims
Intestinal tuberculosis (ITB) and Crohn’s disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same.
Methods
Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL. Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy.
Results
Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55–0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17.
Conclusions
In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.

Citations

Citations to this article as recorded by

Mistakes to avoid in the management of abdominal tuberculosis
Abhirup Chatterjee, Daya Krishna Jha, Aravind Sekar, Vishal Sharma
Expert Review of Anti-infective Therapy.2025; 23(2-4): 197. CrossRef
New diagnostic strategies to distinguish Crohn's disease and gastrointestinal tuberculosis
Himanshu Narang, Saurabh Kedia, Vineet Ahuja
Current Opinion in Infectious Diseases.2024; 37(5): 392. CrossRef
Interferon-gamma release assays as a tool for differential diagnosis of gastrointestinal tuberculosis
Tsvetelina Velikova, Anita Aleksandrova
World Journal of Clinical Cases.2024; 12(27): 6015. CrossRef
Diagnostic yield and technical performance of the novel motorized spiral enteroscopy compared with single-balloon enteroscopy in suspected Crohn's disease: a prospective study (with video)
Partha Pal, Piyush Vishwakarma, Aniruddha Pratap Singh, Palle Manohar Reddy, Mohan Ramchandani, Rupa Banerjee, Anuradha Sekaran, Polina Vijayalaxmi, Hardik Rughwani, Pradev Inavolu, Santosh Darishetty, Pradeep Rebala, Guduru Venkat Rao, Manu Tandan, D. Na
Gastrointestinal Endoscopy.2023; 97(3): 493. CrossRef
Evidence-based approach to diagnosis and management of abdominal tuberculosis
Daya Krishna Jha, Mythili Menon Pathiyil, Vishal Sharma
Indian Journal of Gastroenterology.2023; 42(1): 17. CrossRef
Technical performance and diagnostic yield of motorised spiral enteroscopy compared with single-balloon enteroscopy in suspected Crohn’s disease: a randomised controlled, open-label study (the MOTOR-CD trial)
Partha Pal, Mohan Ramchandani, Rupa Banerjee, Piyush Viswakarma, Aniruddha Pratap Singh, Manohar Reddy, Hardik Rughwani, Rajendra Patel, Anuradha Sekaran, Swathi Kanaganti, Santosh Darisetty, Zaheer Nabi, Jagadish Singh, Rajesh Gupta, Sundeep Lakhtakia, R
Gut.2023; 72(10): 1866. CrossRef

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Miscellaneous

Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis: Saurabh Kedia, Raju Sharma, Sudheer Kumar Vuyyuru, Deepak Madhu, Pabitra Sahu, Bhaskar Kante, Prasenjit Das, Ankur Goyal, Karan Madan, Govind Makharia, Vineet Ahuja; Intest Res 2022;20(2):184-191. Published online May 4, 2021; DOI: https://doi.org/10.5217/ir.2020.00104

Abstract PDF PubReader ePub

Background/Aims
Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB.
Methods
Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs.
Results
Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%.
Conclusions
Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.

Citations

Citations to this article as recorded by

Imaging in Abdominal Tuberculosis
Anuradha Sharma, Ankur Goyal, Devasenathipathy Kandasamy, Saurabh Kedia, Vineet Ahuja, Raju Sharma
Indographics.2024; 03(02): 045. CrossRef
Evidence-based approach to diagnosis and management of abdominal tuberculosis
Daya Krishna Jha, Mythili Menon Pathiyil, Vishal Sharma
Indian Journal of Gastroenterology.2023; 42(1): 17. CrossRef
Risk factors identification of COVID‐19 patients with chronic obstructive pulmonary disease: A retrospective study in Punjab‐Pakistan
Muhammad Muneeb Hassan, M. H. Tahir, Muhammad Ameeq, Farrukh Jamal, John T. Mendy, Christophe Chesneau
Immunity, Inflammation and Disease.2023;[Epub] CrossRef
Strengthening Tuberculosis Services for Children and Adolescents in Low Endemic Settings
Jeffrey R. Starke, Connie Erkens, Nicole Ritz, Ian Kitai
Pathogens.2022; 11(2): 158. CrossRef
Stringent screening strategy significantly reduces reactivation rates of tuberculosis in patients with inflammatory bowel disease on anti‐TNF therapy in tuberculosis endemic region
Peeyush Kumar, Sudheer K. Vuyyuru, Bhaskar Kante, Pabitra Sahu, Sandeep Goyal, Deepak Madhu, Saransh Jain, Mukesh Kumar Ranjan, Sandeep Mundhra, Rithvik Golla, Mukesh Singh, Shubi Virmani, Anvita Gupta, Nidhi Yadav, Mani Kalaivani, Raju Sharma, Prasenjit
Alimentary Pharmacology & Therapeutics.2022; 55(11): 1431. CrossRef

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Inflammatory Bowel Diseases

Prospective validation of CD4⁺CD25⁺FOXP3⁺ T-regulatory cells as an immunological marker to differentiate intestinal tuberculosis from Crohn’s disease: Ritika Rampal, Saurabh Kedia, Mohamad Nahidul Wari, Deepak Madhu, Amit Kumar Singh, Veena Tiwari, V. Pratap Mouli, Srikant Mohta, Govind Makharia, Vineet Ahuja; Intest Res 2021;19(2):232-238. Published online May 8, 2020; DOI: https://doi.org/10.5217/ir.2019.09181

Abstract PDF PubReader ePub

Background/Aims
Crohn’s disease (CD) and intestinal tuberculosis (ITB) remain “difficult-to-differentiate” diseases. We have previously documented peripheral blood frequency of CD4⁺CD25⁺FOXP3⁺ T-regulatory cells (Treg) as a biomarker to differentiate CD and ITB. We tried to validate these results in a larger cohort of CD and ITB patients.
Methods
Seventy treatment naïve patients of CD (n = 23) and ITB (n = 47) (diagnosed by standard criteria) were recruited prospectively from October 2016 to May 2017. Patients with history of antitubercular therapy in the past were excluded. The frequency of Treg cells in peripheral blood was determined by flow cytometry, and compared between CD and ITB patients.
Results
Similar to our previous study, frequency of Treg cells in peripheral blood was significantly increased in ITB as compared to CD patients (40.9 [interquartile range, 33–50] vs. 24.9 [interquartile range, 14.4–29.6], P< 0.001). Further, the receiver operating characteristics curve also showed good diagnostic accuracy with an area under the curve (AUC) of 0.77 (95% confidence interval, 0.65–0.89) and a FOXP3⁺ cutoff value of > 31.3% had a sensitivity and specificity of 83% and 82.6% respectively, to differentiate ITB from CD. Even for the indeterminate cases (n = 33), Treg cell frequency had similar diagnostic accuracy with an AUC of 0.85 (95% confidence interval, 0.68–0.95) and a cutoff of 32.37% had sensitivity and specificity of 87% and 95% respectively, to differentiate ITB from CD.
Conclusions
The current findings validate that the increased frequency of CD4⁺CD25⁺FOXP3⁺ Treg in the peripheral blood can be used as a biomarker with high diagnostic accuracy to differentiate ITB from CD.

Citations

Citations to this article as recorded by

New diagnostic strategies to distinguish Crohn's disease and gastrointestinal tuberculosis
Himanshu Narang, Saurabh Kedia, Vineet Ahuja
Current Opinion in Infectious Diseases.2024; 37(5): 392. CrossRef
Evidence-based approach to diagnosis and management of abdominal tuberculosis
Daya Krishna Jha, Mythili Menon Pathiyil, Vishal Sharma
Indian Journal of Gastroenterology.2023; 42(1): 17. CrossRef
Gut Microbiome in Probable Intestinal Tuberculosis and Changes following Anti-Tuberculosis Treatment
Hyuk Yoon, Young Soo Park, Cheol Min Shin, Nayoung Kim, Dong Ho Lee
Yonsei Medical Journal.2022; 63(1): 34. CrossRef
Single-nucleotide polymorphisms and activities of indoleamine 2,3-dioxygenase isoforms, IDO1 and IDO2, in tuberculosis patients
Tingming Cao, Guangming Dai, Hongqian Chu, Chengcheng Kong, Huijuan Duan, Na Tian, Zhaogang Sun
Hereditas.2022;[Epub] CrossRef
Recent advances in the diagnosis of intestinal tuberculosis
Hasan Maulahela, Marcellus Simadibrata, Erni Juwita Nelwan, Nur Rahadiani, Editha Renesteen, S. W. T. Suwarti, Yunita Windi Anggraini
BMC Gastroenterology.2022;[Epub] CrossRef
Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis
Saurabh Kedia, Raju Sharma, Sudheer Kumar Vuyyuru, Deepak Madhu, Pabitra Sahu, Bhaskar Kante, Prasenjit Das, Ankur Goyal, Karan Madan, Govind Makharia, Vineet Ahuja
Intestinal Research.2022; 20(2): 184. CrossRef
Inflammatory bowel disease in Korea: epidemiology and pathophysiology
Jung Won Lee, Chang Soo Eun
The Korean Journal of Internal Medicine.2022; 37(5): 885. CrossRef
Intestinal tuberculosis or Crohn's disease: Illusion or delusion or allusion
Saurabh Kedia, Vineet Ahuja
JGH Open.2021; 5(2): 177. CrossRef
Deep‐learning system for real‐time differentiation between Crohn's disease, intestinal Behçet's disease, and intestinal tuberculosis
Jung Min Kim, Jun Gu Kang, Sungwon Kim, Jae Hee Cheon
Journal of Gastroenterology and Hepatology.2021; 36(8): 2141. CrossRef
Mycobacterium tuberculosis (MTB) antigen-induced upregulation of interleukin-35 expression in patients with MTB infection: In vitro blockade of the effects of interleukin-35 on T lymphocyte subsets
Hongbin Jiang, Beinian Cui, Jun Zhang
Pathogens and Disease.2021;[Epub] CrossRef

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Review

IBD

Intestinal tuberculosis or Crohn’s disease: a review of the diagnostic models designed to differentiate between these two gastrointestinal diseases: Julajak Limsrivilai, Nonthalee Pausawasdi; Intest Res 2021;19(1):21-32. Published online April 22, 2020; DOI: https://doi.org/10.5217/ir.2019.09142

Abstract PDF PubReader ePub

Differentiating Crohn’s disease (CD) from intestinal tuberculosis (ITB) is a diagnostic dilemma, particularly in regions where ITB is prevalent and CD incidence is increasing, because both diseases can present quite similarly, and diagnostic tests to identify Mycobacterium tuberculosis in tissue samples have rather poor sensitivity. Studies that were conducted to determine the factors that differentiate CD from ITB identified some significant characteristics, but none of those characteristics are exclusive to either ITB or CD. Many diagnostic models or scoring systems that use one to several diagnostic parameters have been proposed to help distinguish these two intestinal diseases. Early models consisted of parameters common to routine clinical practice, such as clinical features, and endoscopic and pathologic findings. The later models also include more advanced diagnostic parameters like high-resolution imaging and serological testing. However, the number and types of parameters differ among diagnostic models, and the systems used to calculate scoring also vary from model to model. Enhanced awareness and understanding of the currently available diagnostic models will help physicians determine which model(s) is/are most suitable for differentiating CD from ITB in their clinical practice.

Citations

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A novel multidisciplinary machine learning approach based on clinical, imaging, colonoscopy, and pathology features for distinguishing intestinal tuberculosis from Crohn’s disease
Baolan Lu, Zengan Huang, Jinjiang Lin, Ruonan Zhang, Xiaodi Shen, Lili Huang, Xinyue Wang, Weitao He, Qiapeng Huang, Jiayu Fang, Ren Mao, Zhoulei Li, Bingsheng Huang, Shi-Ting Feng, Ziying Ye, Jian Zhang, Yangdi Wang
Abdominal Radiology.2024; 49(7): 2187. CrossRef
Ten missteps in the management of inflammatory bowel disease in Asia: An expert report by the Asian Pacific Association of Gastroenterology Working Group on Inflammatory Bowel Disease
Vineet Ahuja, Ida Hilmi, Byong Duk Ye, Khoon Lin Ling, Siew C. Ng, Rupert W. Leong, Peeyush Kumar, Xin Hui Khoo, Govind K. Makharia, Jose Sollano, Pises Pisespongsa, Nazri Mustaffa, Rupa Banerjee, Alex Hwong‐Ruey Leow, Raja Affendi Raja Ali, Sai Wei Chuah
Journal of Gastroenterology and Hepatology.2024; 39(8): 1500. CrossRef
Management of Crohn’s disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023
Jia-Feng Wu, Hsu-Heng Yen, Horng-Yuan Wang, Ting-An Chang, Chung-Hsin Chang, Chen-Wang Chang, Te-Hsin Chao, Jen-Wei Chou, Yenn-Hwei Chou, Chiao-Hsiung Chuang, Wen-Hung Hsu, Tzu-Chi Hsu, Tien-Yu Huang, Tsung-I Hung, Puo-Hsien Le, Chun-Che Lin, Chun-Chi Lin
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Jiaqi Zeng, Guanzhou Zhou, Fei Pan
Journal of Clinical Medicine.2023; 12(2): 445. CrossRef
Interferon-gamma release assay has poor diagnostic accuracy in differentiating intestinal tuberculosis from Crohn’s disease in tuberculosis endemic areas
Karan Sachdeva, Peeyush Kumar, Bhaskar Kante, Sudheer K. Vuyyuru, Srikant Mohta, Mukesh K. Ranjan, Mukesh K. Singh, Mahak Verma, Govind Makharia, Saurabh Kedia, Vineet Ahuja
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Pooja KC, Madhur Bhattarai, Subodh Adhikari, Prakriti Parajuli, Sujata Bhandari, Himal Bikram Bhattarai, Niraj Kumar Sharma, Shailendra Karki, Suryakiran Acharya, Bibhusan Basnet
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Infectious complications in patients with inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 8th Asian Organization for Crohn’s and Colitis meeting
Yu Kyung Jun, Seong-Joon Koh, Dae Seong Myung, Sang Hyoung Park, Choon Jin Ooi, Ajit Sood, Jong Pil Im
Intestinal Research.2023; 21(3): 353. CrossRef
Differentiating Crohn’s disease from intestinal tuberculosis using a fusion correlation neural network
Yinghao Chen, Ying Li, Minfeng Wu, Fanggen Lu, Muzhou Hou, Yani Yin
Knowledge-Based Systems.2022; 244: 108570. CrossRef
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Yong Eun Park, Hye Su Moon, Dongeun Yong, Hochan Seo, Jinho Yang, Tae-Seop Shin, Yoon-Keun Kim, Jin Ran Kim, Yoo Na Lee, Young-Ho Kim, Joo Sung Kim, Jae Hee Cheon
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Inflammatory bowel disease in Korea: epidemiology and pathophysiology
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Latent and Active Tuberculosis Infection in Patients with Inflammatory Bowel Disease
Byung Chul Jin, Hee Jin Moon, Sang Wook Kim
The Korean Journal of Gastroenterology.2022; 80(2): 72. CrossRef
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N. Van Moorter, J. Jaekers, E. André, W. Meersseman, A. Wilmer
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An Outcome-Based Composite Approach for the Diagnosis of Intestinal Tuberculosis: A Pilot Study from a Tertiary Care Centre in South India
Roopa Rachel Paulose, V Anil Kumar, Aparna Sharma, Aditi Damle, Divya Saikumar, Abish Sudhakar, Anoop K Koshy, Rama P Venu
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Original Articles

Inflammatory bowel diseases

Concordance between tuberculin skin test and interferon-gamma release assay for latent tuberculosis screening in inflammatory bowel disease: Saad Alrajhi, Pascale Germain, Myriam Martel, Peter Lakatos, Talat Bessissow, Talal Al-Taweel, Waqqas Afif; Intest Res 2020;18(3):306-314. Published online March 20, 2020; DOI: https://doi.org/10.5217/ir.2019.00116

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Latent tuberculosis screening is mandatory prior to initiating anti-tumor necrosis factor (anti-TNF) medications. Guidelines recommend interferon-gamma release assays (IGRA) as first line screening method for the general population. Studies provided conflicting evidence on IGRA and tuberculin skin test (TST) performance in inflammatory bowel disease (IBD) patients. We assessed test concordance and the effects of immunosuppression on their performance in IBD patients.
Methods
We searched MEDLINE, Embase and Cochrane databases (2011–2018) for studies testing TST and IGRA in IBD. Primary outcome was TST and IGRA concordance. Secondary outcomes were effects of immunosuppressive therapy on performance. Immunosuppression defined as either steroids, thiopurine, methotrexate or cyclosporine use. We used the pooled random effects model to adjust for heterogeneity analyzed using (I²–Q statistics). We compared the fixed model to exclude smaller study effects.
Results
Sixteen studies (2,488 patients) were included. Pooled TST and IGRA concordance was 85% (95% confidence interval [CI], 81%–88%; P=0.01). Effects of immunosuppression were reported in 8 studies (814 patients). The odds ratio of testing positive by IGRA decreased to 0.57 if immunosuppressed (95% CI, 0.31–1.03; P=0.06). The odds ratio of testing positive by TST if immunosuppressed was 1.14 (95% CI, 0.61–2.12; P=0.69). The fixed model yielded similar results, however the negative effect of immunosuppression on IGRA reached statistical significance (P=0.01).
Conclusions
While concordance was 85% between TST and IGRA, the performance of IGRA seems to be negatively affected by immunosuppression. Given the importance of detecting latent tuberculosis prior to anti-TNF initiation, further randomized controlled trials comparing the performance of TST and IGRA in IBD patients are needed.

Citations

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IBD

High risk of tuberculosis during infliximab therapy despite tuberculosis screening in inflammatory bowel disease patients in India: Ashish Agarwal, Saurabh Kedia, Saransh Jain, Vipin Gupta, Sawan Bopanna, Dawesh P Yadav, Sandeep Goyal, Venigalla Pratap Mouli, Rajan Dhingra, Govind Makharia, Vineet Ahuja; Intest Res 2018;16(4):588-598. Published online October 10, 2018; DOI: https://doi.org/10.5217/ir.2018.00023

Abstract PDF PubReader ePub

Background/Aims
The data on the risk of tuberculosis (TB) reactivation with infliximab (IFX) in patients with inflammatory bowel disease (IBD) from TB endemic countries, like India, is limited. The risk of TB reactivation on IFX and its predictors in patients with IBD was assessed.
Methods
This retrospective review included consecutive patients with IBD who received IFX, and were on follow-up from January 2005 to November 2017. The data was recorded on age/disease duration, indications for IFX, screening for latent tuberculosis (LTB) before IFX, response to IFX, incidence and duration when TB developed after IFX, and type of TB (pulmonary [PTB]/extra-pulmonary [EPTB]/disseminated).
Results
Of 69 patients (22 ulcerative colitis/47 Crohn’s disease; mean age, 35.6±14.5 years; 50.7% males; median follow-up duration after IFX, 19 months [interquartile range, 5.5–48.7 months]), primary non-response at 8 weeks and secondary loss of response at 26 and 52 weeks were seen in 14.5%, 6% and 15% patients respectively. Prior to IFX, all patients were screened for LTB, 8 (11.6%) developed active TB (disseminated, 62.5%; EPTB, 25%; PTB, 12.5%) after a median of 19 weeks (interquartile range, 14.0–84.5 weeks) of IFX. Of these 8 patients’ none had LTB, even when 7 of 8 were additionally screened with contrast-enhanced chest tomography. Though not statistically significant, more patients with Crohn’s disease than ulcerative colitis (14.9% vs. 4.5%, P=0.21), and those with past history of TB (25% vs. 9.8%, P=0.21), developed TB. Age, gender, disease duration, or extraintestinal manifestations could not predict TB reactivation.
Conclusions
There is an extremely high rate of TB with IFX in Indian patients with IBD. Current screening techniques are ineffective and it is difficult to predict TB after IFX.

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IBD

Selective M1 macrophage polarization in granuloma-positive and granuloma-negative Crohn's disease, in comparison to intestinal tuberculosis: Prasenjit Das, Ritika Rampal, Sonakshi Udinia, Tarun Kumar, Sucharita Pilli, Nahid Wari, Imtiaz Khan Ahmed, Saurabh Kedia, Siddhartha Datta Gupta, Dhiraj Kumar, Vineet Ahuja; Intest Res 2018;16(3):426-435. Published online July 27, 2018; DOI: https://doi.org/10.5217/ir.2018.16.3.426

Abstract PDF PubReader ePub

Background/Aims

Classical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB).

Methods

Colonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1_φ marker) and CD163/CD68 (an M2_φ marker), and the ratio of M1_φ to M2_φ was assessed. To establish the innate nature of macrophage polarization, we analyzed the extent of mitochondrial depolarization, a key marker of inflammatory responses, in monocyte-derived macrophages obtained from CD and iTB patients, following interferon-γ treatment.

Results

M1_φ polarization was more prominent in CD biopsies (P=0.002) than in iTB (P=0.2) and control biopsies. In granuloma-positive biopsies, including those in CD, M1_φ predominance was significant (P=0.001). In iTB, the densities of M1_φ did not differ between granuloma-positive and granuloma-negative biopsies (P=0.1). Interestingly, higher M1_φ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients.

Conclusions

Proinflammatory M1_φ polarization was more common in colonic mucosa of CD patients, especially in the presence of mucosal granulomas. Further characterization of the innate immune system could help in clarifying the pathology of iTB and CD.

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IBD

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment: Dong Il Park, Tadakazu Hisamatsu, Minhu Chen, Siew Chien Ng, Choon Jin Ooi, Shu Chen Wei, Rupa Banerjee, Ida Normiha Hilmi, Yoon Tae Jeen, Dong Soo Han, Hyo Jong Kim, Zhihua Ran, Kaichun Wu, Jiaming Qian, Pin-Jin Hu, Katsuyoshi Matsuoka, Akira Andoh, Yasuo Suzuki, Kentaro Sugano, Mamoru Watanabe, Toshifumi Hibi, Amarender S. Puri, Suk-Kyun Yang; Intest Res 2018;16(1):4-16. Published online January 18, 2018; DOI: https://doi.org/10.5217/ir.2018.16.1.4

Abstract PDF PubReader ePub

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommendaduring anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

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Special Review: Consensus on TB in IBD

IBD

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: management: Dong Il Park, Tadakazu Hisamatsu, Minhu Chen, Siew Chien Ng, Choon Jin Ooi, Shu Chen Wei, Rupa Banerjee, Ida Normiha Hilmi, Yoon Tae Jeen, Dong Soo Han, Hyo Jong Kim, Zhihua Ran, Kaichun Wu, Jiaming Qian, Pin-Jin Hu, Katsuyoshi Matsuoka, Akira Andoh, Yasuo Suzuki, Kentaro Sugano, Mamoru Watanabe, Toshifumi Hibi, Amarender S. Puri, Suk-Kyun Yang; Intest Res 2018;16(1):17-25. Published online January 18, 2018; DOI: https://doi.org/10.5217/ir.2018.16.1.17

Abstract PDF PubReader ePub

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

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Original Articles

Predictive factors for malignancy in undiagnosed isolated small bowel strictures: Ujjwal Sonika, Sujeet Saha, Saurabh Kedia, Nihar Ranjan Dash, Sujoy Pal, Prasenjit Das, Vineet Ahuja, Peush Sahni; Intest Res 2017;15(4):518-523. Published online October 23, 2017; DOI: https://doi.org/10.5217/ir.2017.15.4.518

Abstract PDF PubReader ePub

Background/Aims

Patients with small bowel strictures have varied etiologies, including malignancy. Little data are available on the demographic profiles and etiologies of small bowel strictures in patients who undergo surgery because of intestinal obstruction but do not have a definitive pre-operative diagnosis.

Methods

Retrospective data were analyzed for all patients operated between January 2000 and October 2014 for small bowel strictures without mass lesions and a definite diagnosis after imaging and endoscopic examinations. Demographic parameters, imaging, endoscopic, and histological data were extracted from the medical records. Univariate and multivariate analyses were conducted to identify factors that could differentiate between intestinal tuberculosis (ITB) and Crohn's disease (CD) and between malignant and benign strictures.

Results

Of the 7,425 reviewed medical records, 89 met the inclusion criteria. The most common site of strictures was the proximal small intestine (41.5%). The most common histological diagnoses in patients with small bowel strictures were ITB (26.9%), CD (23.5%), non-specific strictures (20.2%), malignancy (15.5%), ischemia (10.1%), and other complications (3.4%). Patients with malignant strictures were older than patients with benign etiologies (47.6±15.9 years vs. 37.4±16.4 years, P=0.03) and age >50 years had a specificity for malignant etiology of 80%. Only 7.1% of the patients with malignant strictures had more than 1 stricture and 64% had proximally located strictures. Diarrhea was the only factor that predicted the diagnosis of CD 6.5 (95% confidence interval, 1.10–38.25; P=0.038) compared with the diagnosis of ITB.

Conclusions

Malignancy was the cause of small bowel strictures in approximately 16% patients, especially among older patients with a single stricture in the proximal location. Empirical therapy should be avoided and the threshold for surgical resection is low in these patients.

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Evaluation of Xpert MTB/RIF assay performance in the diagnosis of abdominal tuberculosis: Suraj Kumar, Sawan Bopanna, Saurabh Kedia, Pratap Mouli, Rajan Dhingra, Rajesh Padhan, Mikashmi Kohli, Jigyasa Chaubey, Rohini Sharma, Prasenjit Das, S Dattagupta, Govind Makharia, SK Sharma, Vineet Ahuja; Intest Res 2017;15(2):187-194. Published online April 27, 2017; DOI: https://doi.org/10.5217/ir.2017.15.2.187

Abstract PDF PubReader ePub

Background/Aims

The use of genetic probes for the diagnosis of pulmonary tuberculosis (TB) has been well described. However, the role of these assays in the diagnosis of intestinal tuberculosis is unclear. We therefore assessed the diagnostic utility of the Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay, and estimated the prevalence of multidrug-resistant (MDR) TB in the Indian population.

Methods

Of 99 patients recruited, 37 had intestinal TB; two control groups comprised 43 with Crohn's disease (CD) and 19 with irritable bowel syndrome. Colonoscopy was performed before starting any therapy; mucosal biopsies were subjected to histopathology, acid-fast bacilli staining, Lowenstein-Jensen culture, and nucleic acid amplification testing using the Xpert MTB/RIF assay. Patients were followed up for 6 months to confirm the diagnosis and response to therapy. A composite reference standard was used for diagnosis of TB and assessment of the diagnostic utility of the Xpert MTB/RIF assay.

Results

Of 37 intestinal TB patients, the Xpert MTB/RIF assay was positive in three of 37 (8.1%), but none had MDR-TB. The sensitivity, specificity, positive predictive value, and negative predictive value of the Xpert MTB/RIF assay was 8.1%, 100%, 100%, and, 64.2%, respectively.

Conclusions

The Xpert MTB/RIF assay has low sensitivity but high specificity for intestinal TB, and may be helpful in endemic tuberculosis areas, when clinicians are faced with difficulty differentiating TB and CD. Based on the Xpert MTB/RIF assay, the prevalence of intestinal MDR-TB is low in the Indian population.

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Systematic Review

Accuracy of computed tomographic features in differentiating intestinal tuberculosis from Crohn's disease: a systematic review with meta-analysis: Saurabh Kedia, Raju Sharma, Vishnubhatla Sreenivas, Kumble Seetharama Madhusudhan, Vishal Sharma, Sawan Bopanna, Venigalla Pratap Mouli, Rajan Dhingra, Dawesh Prakash Yadav, Govind Makharia, Vineet Ahuja; Intest Res 2017;15(2):149-159. Published online April 27, 2017; DOI: https://doi.org/10.5217/ir.2017.15.2.149

Abstract PDF PubReader ePub

Abdominal computed tomography (CT) can noninvasively image the entire gastrointestinal tract and assess extraintestinal features that are important in differentiating Crohn's disease (CD) and intestinal tuberculosis (ITB). The present meta-analysis pooled the results of all studies on the role of CT abdomen in differentiating between CD and ITB. We searched PubMed and Embase for all publications in English that analyzed the features differentiating between CD and ITB on abdominal CT. The features included comb sign, necrotic lymph nodes, asymmetric bowel wall thickening, skip lesions, fibrofatty proliferation, mural stratification, ileocaecal area, long segment, and left colonic involvements. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (DOR) were calculated for all the features. Symmetric receiver operating characteristic curve was plotted for features present in >3 studies. Heterogeneity and publication bias was assessed and sensitivity analysis was performed by excluding studies that compared features on conventional abdominal CT instead of CT enterography (CTE). We included 6 studies (4 CTE, 1 conventional abdominal CT, and 1 CTE+conventional abdominal CT) involving 417 and 195 patients with CD and ITB, respectively. Necrotic lymph nodes had the highest diagnostic accuracy (sensitivity, 23%; specificity, 100%; DOR, 30.2) for ITB diagnosis, and comb sign (sensitivity, 82%; specificity, 81%; DOR, 21.5) followed by skip lesions (sensitivity, 86%; specificity, 74%; DOR, 16.5) had the highest diagnostic accuracy for CD diagnosis. On sensitivity analysis, the diagnostic accuracy of other features excluding asymmetric bowel wall thickening remained similar. Necrotic lymph nodes and comb sign on abdominal CT had the best diagnostic accuracy in differentiating CD and ITB.

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Case Report

Rectal tuberculosis after infliximab therapy despite negative screening for latent tuberculosis in a patient with ulcerative colitis: Jatinderpal Singh, Amarender S Puri, Sanjeev Sachdeva, Puja Sakhuja, Kulandaivelu Arivarasan; Intest Res 2016;14(2):183-186. Published online April 27, 2016; DOI: https://doi.org/10.5217/ir.2016.14.2.183

Abstract PDF PubReader ePub

Tumor necrosis factor-α inhibitors are now considered as standard therapy for patients with severe inflammatory bowel disease who do not respond to corticosteroids, but they carry a definite risk of reactivation of tuberculosis. We present a case in which a patient with inflammatory bowel disease developed a de novo tuberculosis infection after the start of anti-tumor necrosis factor-α treatment despite showing negative results in tuberculosis screening. Although there are many case reports of pleural, lymph nodal and disseminated tuberculosis following infliximab therapy, we present the first case report of rectal tuberculosis following infliximab therapy.

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Dong II Park, Tadakazu Hisamatsu, Minhu Chen, Siew Chien Ng, Choon Jin Ooi, Shu Chen Wei, Rupa Banerjee, Ida Normiha Hilmi, Yoon Tae Jeen, Dong Soo Han, Hyo Jong Kim, Zhihua Ran, Kaichun Wu, Jiaming Qian, Pin‐Jin Hu, Katsuyoshi Matsuoka, Akira Andoh, Yasu
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Original Article

Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease: Jang Wook Lee, Chang Hwan Choi, Ji Hoon Park, Jeong Wook Kim, Sang Bum Kang, Ja Seol Koo, Young-Ho Kim, You Sun Kim, Young Eun Joo, Sae Kyung Chang; Intest Res 2016;14(2):146-151. Published online April 27, 2016; DOI: https://doi.org/10.5217/ir.2016.14.2.146

Abstract PDF PubReader ePub

Background/Aims

Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy.

Methods

Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB.

Results

The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2–36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients.

Conclusions

Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB.

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Statement

Seminar Report From the 2014 Taiwan Society of Inflammatory Bowel Disease (TSIBD) Spring Forum (May 24th, 2014): Crohn's Disease Versus Intestinal Tuberculosis Infection: Meng-Tzu Weng, Shu-Chen Wei, Chun-Che Lin, Yuk-Min Tsang, Chia-Tung Shun, Jann-Yuan Wang, Ming-Jium Shieh, Cheng-Yi Wang, Jau-Min Wong; Intest Res 2015;13(1):6-10. Published online January 29, 2015; DOI: https://doi.org/10.5217/ir.2015.13.1.6

Abstract PDF PubReader

Since Taiwan is an endemic area for tuberculosis (TB), differential diagnosis between the intestinal TB and Crohn's disease is an important issue. The steering committee of Taiwan Society of Inflammatory Bowel Disease (TSIBD) has arranged a seminar accordingly on May 24th, 2014 and the different point of views by gastroenterologist, radiologist, pathologist and infectious disease specialist were suggested to help the proper diagnosis and management of these two diseases.

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Review

Diagnosis and Treatment of Latent Tuberculosis Infection in Patients with Inflammatory Bowel Diseases due to Initiation of Anti-Tumor Necrosis Factor Therapy: Tae Sun Shim; Intest Res 2014;12(1):12-19. Published online January 28, 2014; DOI: https://doi.org/10.5217/ir.2014.12.1.12

Abstract PDF PubReader

Patients with intractable inflammatory bowel diseases (IBD) are increasingly being treated with anti-tumor necrosis factor (TNF) agents and are at increased risk of developing tuberculosis (TB). Therefore, diagnosis and treatment of latent TB infection (LTBI) is recommended in patients due to the initiation of anti-TNF therapy. Traditionally, LTBI has been diagnosed on the basis of clinical factors and a tuberculin skin test. Recently, interferon-gamma releasing assays (IGRAs) that can detect TB infection have become available. Considering the high-risk of developing TB in patients on anti-TNF therapy, the use of both a tuberculin skin test and an IGRA should be considered to detect and treat LTBI in patients with IBD due to the initiation of anti-TNF therapy. The traditional LTBI treatment regimen has consisted of isoniazid monotherapy for 9 months. However, shorter regimens such as 4 months of rifampicin or 3 months of isoniazid/rifampicin have been used increasingly to improve treatment completion rates. In this review, the incidence of TB and the prevalence of LTBI in patients with IBD will be briefly described, as well as methods for diagnosing latent and active TB before anti-TNF therapy, current LTBI treatment regimens, recommendations for managing TB that develops during anti-TNF therapy, the necessity of regular monitoring to detect new TB infection, and the re-initiation of anti-TNF therapy in patients who develop TB.

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