Validation of Scoring Systems for Differentiating Intestinal Tuberculosis from Crohn's Disease

Validation of Scoring Systems for Differentiating Intestinal Tuberculosis from Crohn's Disease Utilizing Clinical, Endoscopic, and Interferon-gamma Releasing Assay in Asian Population

Differentiating CD from intestinal tuberculosis (ITB) is difficult due to the low sensitivities of currently available diagnostic tests. The Asia-Pacific guideline recommends anti-tuberculous therapy (ATT) for 8-12 weeks in patients with diagnostic uncertainty due to the risk of disseminated tuberculosis if patients with ITB are misdiagnosed with CD, and are prescribed immunosuppressive therapy. However, treatment with ATT has many side effects and may delay treatment in patients with CD, and this may cause severe relapse and developing complications. Many studies found that some clinical, endoscopy, pathology, radiology, and serology findings can help to improve diagnostic accuracy in these patients. However, no single diagnostic parameter can distinguish between CD and ITB. As a result, many models were developed that include various factors and modalities, and many of those models have been reported to have high performance. However, the number of studies performed to validate those models externally was limited. Correspondingly, this study is designed to prospectively validate models that integrate more advanced parameters (e.g., IGRA, CT enterography findings) with clinical, endoscopic, or pathological findings. However, it aims mainly to evaluate the model integrating clinical, endoscopic, and serological variables since CT enterography and pathological interpretation require experienced radiologists and pathologists but they are not available in many centers.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease; Intestinal Tuberculosis; Differential Diagnosis
• Intervention / Treatment: Diagnostic test: interferon gamma releasing assay (IGRA)

Detailed Description

Crohn's disease (CD) incidence has been increasing in Asia over the last few decades [1]. Moreover, differentiating CD from intestinal tuberculosis (ITB) is difficult due to the low sensitivities of currently available diagnostic tests. The 5.3- 37.5% sensitivity of acid-fast bacilli (AFB) specimen staining, the 23%-46% sensitivity of mycobacterial culture, and the 36.4-67.9% sensitivity of tissue polymerase chain reaction (PCR) are all too low to confidently distinguish between these two conditions and exclude a diagnosis of ITB. The Asia-Pacific guideline recommends anti-tuberculous therapy (ATT) for 8-12 weeks in patients with diagnostic uncertainty due to the risk of disseminated tuberculosis if patients with ITB are misdiagnosed with CD, and are prescribed immunosuppressive therapy. However, treatment with ATT has many side effects and may delay treatment in patients with CD, and this may cause severe relapse and developing complications. In response, many studies were conducted to identify and classify characteristics that can help to distinguish between these two diseases. Those studies found that some clinical, endoscopy, pathology, radiology, and serology findings can help to improve diagnostic accuracy in these patients. However, no single diagnostic parameter can distinguish between CD and ITB. As a result, many models were developed that include various factors and modalities, and many of those models have been reported to have high performance. However, the number of studies performed to externally validate those models was limited.

To address this inadequacy, J Limsrivilai, et al. conducted a multicenter retrospective study comparing the ability of each different diagnostic model consisting of different combinations of basic clinical, endoscopic, and pathologic parameters affordable to resource-limited healthcare settings at differentiating CD and ITB patients. In the study, several differentiating models were included and applied to a cohort of 590 patients from Thailand and Hong Kong to validate the models. The results from the study concluded that the accuracy of a differentiating model is directly correlated with the number of diagnostic modalities and variables of the model with the ITBvsCD-CEP model, which includes 22 variables from clinical, endoscopy, and pathology parameters, demonstrating the highest AUROC as high as 0.887. Although the model demonstrated such impressive diagnostic ability, its application in real-life clinical practice has remained controversial as around 10% of ITB patients would still be misdiagnosed and thus receive the wrong treatments. Integrating more diagnostic modalities, such as interferon gamma-releasing assay (IGRA) and CT enterography, may be helpful.

Correspondingly, this study is designed to prospectively validate models that integrate more advanced parameters (e.g., IGRA, CT enterography findings) with clinical, endoscopic, or pathological findings. However, it aims mainly to evaluate the model integrating clinical, endoscopic, and serological variables since CT enterography and pathological interpretation require experienced radiologists and pathologists but they are not available in many centers.

• Study Type: Observational
• Enrollment (Estimated): 84

Contacts and Locations

• Study Contact: Name: Julajak Limsrivilai; Phone Number: +66814968895; Email: alimsrivilai@gmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Not yet recruiting
    • Gastroenterology division, Faculty of Medicine, Siriraj Hospital, Mahidol University
    • Contact: Julajak Limsrivilai, MD; Phone Number: +66814968895; Email: alimsrivilai@gmail.com
    • Contact: Julajak Limsrivilai
  • Bangkok
    • Bangkok Noi, Bangkok, Thailand, 10700
      • Recruiting
      • Assoc. Prof. Julajak Limsrivilai, MD
      • Contact: Onuma Sattayalertyanyong; Phone Number: +66816165390; Email: onuma.gimed@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients who had clinical symptoms suspicious of either Crohn's disease or intestinal tuberculosis are eligible.

Description

Inclusion Criteria:

1. Patients ages 18 years or older
2. Undergoing colonoscopy and found ileal or colonic ulcers
3. Have ileal and/or colonic tissue sent for mycobacterial tests, including stain for AFB, PCR, and culture
4. Diagnosed with either intestinal tuberculosis or Crohn's disease a. Criteria of intestinal tuberculosis diagnosis includes any of following: i. Presence of caseating granuloma on pathological examination of specimens ii. Presence of acid-fast bacilli on pathological examination of specimens iii. PCR positive for Mycobacterium tuberculosis iv. Tissue culture growing organisms consistent with Mycobacterium tuberculosis v. Negative results in i to iv but response to empirical treatment with antituberculous therapy All are required to have clinical and endoscopic response to antituberculous therapy (ATT) treatment b. Diagnosis of Crohn's disease is based on clinical, endoscopic, pathological, and/or radiological findings which is confirmed by clinical & endoscopic response to Crohn's disease treatment

Exclusion Criteria:

1. Patients with ileal/colonic ulcers caused by other diseases

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Crohn's disease; Patients who were diagnosed Crohn's disease - Diagnosis of Crohn's disease is based on clinical, endoscopic, pathological, and/or radiological findings which is confirmed by clinical & endoscopic response to Crohn's disease treatment	Diagnostic test: interferon gamma releasing assay (IGRA); All patients who suspected CD or TB will be tested for interferon-gamma releasing assay. An interferon-gamma release assay is a blood test that measures the body's immune response to Mycobacterium tuberculosis, the bacteria that causes tuberculosis.
Intestinal tuberculosis; Patients who were diagnosed intestinal tuberculosis.; Criteria of intestinal tuberculosis diagnosis includes any of following:i. Presence of caseating granuloma on pathological examination of specimens ii. Presence of acid-fast bacilli on pathological examination of specimens iii. PCR positive for Mycobacterium tuberculosis iv. Tissue culture growing organisms consistent with Mycobacterium tuberculosis v. Negative results in i to iv but response to empirical treatment with antituberculous therapy; All are required to have clinical and endoscopic response to antituberculous therapy (ATT) treatment	Diagnostic test: interferon gamma releasing assay (IGRA); All patients who suspected CD or TB will be tested for interferon-gamma releasing assay. An interferon-gamma release assay is a blood test that measures the body's immune response to Mycobacterium tuberculosis, the bacteria that causes tuberculosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of the ITBvsCD model	The ITBvsCD model performance in differentiating Crohns disease from intestinal tuberculosis will be evaluated by area under the receiver operating characteristic (ROC) curve.	with 4 weeks of colonoscopy

Collaborators and Investigators

• Sponsor: Mahidol University
• Collaborators: Korean Association for the Study of Intestinal Diseases
• Investigators: Principal Investigator: Julajak Limsrivilai, Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: June 9, 2024
• First Submitted That Met QC Criteria: October 4, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: October 4, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Crohn Disease; Intestinal tuberculosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Inflammatory Bowel Diseases; Tuberculosis; Crohn Disease; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons; Interferon-gamma
• Other Study ID Numbers: Si212/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No