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 ) 대한장연구학회 2017 Intestinal Research Vol.15 No.2

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. (Intest Res 2017;15:149-159)

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 ) 대한장연구학회 2022 Intestinal Research Vol.20 No.2

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. (Intest Res 2022;20:184-191)

Management of inflammatory bowel disease in older persons: evolving paradigms

( Saurabh Kedia ),( Jimmy K. Limdi ),( Vineet Ahuja ) 대한장연구학회 2018 Intestinal Research Vol.16 No.2

The incidence and prevalence of inflammatory bowel disease (IBD) is increasing, and considering the aging population, this number is set to increase further in the future. The clinical features and natural history of elderly-onset IBD have many similarities with those of IBD in younger patients, but with significant differences including a broader differential diagnosis. The relative lack of data specific to elderly patients with IBD, often stemming from their typical exclusion from clinical trials, has made clinical decision-making somewhat challenging. Treatment decisions in elderly patients with IBD must take into account age-specific concerns such as comorbidities, locomotor and cognitive function, and polypharmacy, to set realistic treatment targets in order to enable personalized treatment and minimize harm. Notwithstanding paucity of clinical data, recent studies have provided valuable insights, which, taken together with information gleaned from previous studies, can broaden our understanding of IBD. These insights may contribute to the development of paradigms for the holistic and, when possible, evidence-based management of this potentially vulnerable population and are the focus of this review. (Intest Res 2018;16:194-208)

Are Truelove and Witts criteria for diagnosing acute severe colitis relevant for the Indian population?A prospective study

Saransh Jain,Saurabh Kedia,Sawan Bopanna,Dawesh P Yadav,Sandeep Goyal,Peush Sahni,Sujoy Pal,Nihar Ranjan Dash,Govind Makharia,Simon P. L. Travis,Vineet Ahuja 대한장연구학회 2018 Intestinal Research Vol.16 No.1

Background/Aims: Truelove and Witts criteria have been used to define acute severe colitis since the 1950s. However, hemoglobin(an additional criterion of the definition) levels in the general population in developing countries are lower than in the population of developed countries. We aimed to determine the relevance of Truelove and Witts criteria in the Indianpopulation. Methods: Consecutive patients with acute severe colitis satisfying the Truelove and Witts criteria, hospitalized ata single center between April 2015 and December 2016 were included. All patients received intravenous corticosteroids and 16 required colectomy. The hemoglobin levels at admission were subsequently excluded from the classification criteria, and the effect this had on the criteria for diagnosis was determined. Results: Out of 61 patients of acute severe colitis diagnosed according to the original Truelove and Witts criteria, 12 patients (20%) had 1 additional criterion, 33 (54%) had 2 additionalcriteria and 16 (26%) had 3 or more additional criteria in addition to 6 or more blood stained stools on admission. On excludinghemoglobin as an additional criterion from the Truelove and Witts definition, all patients still met the criteria for acute severecolitis. Conclusions: Truelove and Witts criteria can be used to define acute severe colitis in India, despite lower mean hemoglobinin the native population.

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 A 대한장연구학회 2018 Intestinal Research Vol.16 No.4

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. (Intest Res 2018;16:588-598)

The practice of fecal microbiota transplantation in inflammatory bowel disease

Umang Arora,Saurabh Kedia,Vineet Ahuja 대한장연구학회 2024 Intestinal Research Vol.22 No.1

Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn’s disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.

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 ) 대한장연구학회 2021 Intestinal Research Vol.19 No.2

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. (Intest Res 2021;19:232-238)

Familial aggregation of inflammatory bowel disease in patients with ulcerative colitis

( Akshita Gupta ),( Sawan Bopanna ),( Saurabh Kedia ),( Dawesh Prakash Yadav ),( Sandeep Goyal ),( Saransh Jain ),( Govind Makharia ),( Vineet Ahuja ) 대한장연구학회 2017 Intestinal Research Vol.15 No.3

Background/Aims: Familial occurrence of inflammatory bowel disease (IBD) is well documented. Reports from Western countries have shown a higher familial occurrence of ulcerative colitis (UC) in first- and second-degree relatives than that in the Asian UC population. No data are currently available from the Indian subcontinent in this regard. We present our data on the familial aggregation of UC. Methods: Records of patients with UC followed at the Inflammatory Bowel Disease Clinic at the All India Institute of Medical Sciences, New Delhi from August 2004 to January 2016 were reviewed. Details regarding the prevalence of family history and characteristics of these patients were recorded. Affected family members were contacted and disease characteristics were noted for assessment of familial aggregation. Results: Of the 2,058 UC patients included in the analysis, a positive family history of IBD was confirmed in 31 patients (1.5%), 24 (77.4%) of whom had only first-degree relatives affected. All the affected relatives had UC and none had Crohn`s disease. Among first-degree relatives, siblings were found to have the highest prevalence of IBD (53.3%), followed by parents (26.7%). Conclusions: The probability of occurrence of IBD in family members of affected North Indian UC patients is lower than that reported in Western populations. (Intest Res 2017;15:388-394)

Use of thiopurines in inflammatory bowel disease: an update

( Arshdeep Singh ),( Ramit Mahajan ),( Saurabh Kedia ),( Amit Kumar Dutta ),( Abhinav Anand ),( Charles N. Bernstein ),( Devendra Desai ),( C. Ganesh Pai ),( Govind Makharia ),( Harsh Vardhan Tevethia 대한장연구학회 2022 Intestinal Research Vol.20 No.1

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential. (Intest Res 2022;20:11-30)

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 ) 대한장연구학회 2017 Intestinal Research Vol.15 No.4

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. (Intest Res 2017;15:518-523)