The Ewha Medical Journal
Ewha Womans University School Medicine
Case Report

Differentiating between Intestinal Tuberculosis and Crohn’s Disease May Be Complicated by Multidrug-resistant Mycobacterium tuberculosis

Seung Wook Honghttps://orcid.org/0000-0003-1440-9950, Sang Hyoung Parkhttps://orcid.org/0000-0002-5366-5749, Byong Duk Yehttps://orcid.org/0000-0001-6647-6325, Suk-Kyun Yanghttps://orcid.org/0000-0003-2772-2575
Corresponding author Suk-Kyun Yang Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: 82-2-3010-3901, Fax: 82-2-485-5782 E-mail: sky@amc.seoul.kr

Copyright © 2021 Ewha Womans University School of Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: May 11, 2021; Revised: Jun 16, 2021; Accepted: Jul 19, 2021

Published Online: Jul 31, 2021

Abstract

Differentiating between intestinal tuberculosis (ITB) and Crohn’s disease (CD) remains a challenge for gastroenterologists. In Asia, where the prevalence of tuberculosis is relatively high and the incidence of CD is rapidly increasing, this issue is crucial. Here we report a case that was initially misdiagnosed as CD, subsequently showed no response to empirical first-line anti-tuberculosis medication, and was finally diagnosed with multidrug-resistant ITB. This case reminds physicians that multidrug-resistant ITB may complicate distinguishing between ITB and CD.

Keywords: Crohn’s disease; Gastrointestinal tuberculosis; Multidrug-resistant tuberculosis

Introduction

Differentiating between intestinal tuberculosis (ITB) and Crohn’s disease (CD) remains challenging for gastroenterologists, although new technologies such as endoscopic molecular imaging have been developed for inflammatory bowel diseases [1]. In contrast to pulmonary tuberculosis (TB), the issue of drug resistance has rarely been addressed in ITB [2,3]. Apart from treatment difficulties, multidrug-resistant (MDR) Mycobacterium tuberculosis may complicate the differentiation between ITB and CD.

Here we report the case of a 50-year-old female who was initially misdiagnosed as CD, subsequently showed no endoscopic response to 11-week treatment with first-line anti-TB drugs, and was finally diagnosed with MDR ITB on a drug susceptibility test. In this case report, we aim to remind physicians that MDR ITB may complicate distinguishing between ITB and CD.

Case

A 50-year-old female with a history of constipation lasting for more than a year visited an outpatient clinic. She had undergone a colonoscopy at another hospital and treatment with 5-aminosalicylic acid under the diagnosis of CD. Her symptom did not improve despite this treatment for about a year. She reported no gastrointestinal symptoms except constipation and denied any respiratory symptoms. She had no history of pulmonary TB. A chest X-ray was unremarkable.

Colonoscopy conducted at the other hospital revealed multiple transverse ulcerations in the ascending colon and no remarkable findings in the rest of the colon (Fig. 1A). Since endoscopic findings corresponded to typical endoscopic features of ITB, empirical anti-TB treatment was initiated with isoniazid 300 mg/day, rifampin 600 mg/day, pyrazinamide 1.5 g/day, and ethambutol 1.0 g/day. At 11 weeks after the commencement of the first-line anti-TB drug treatment, a colonoscopy was performed to evaluate the endoscopic response. Multiple transverse ulcerations were still visible in the ascending colon, suggesting no endoscopic improvement (Fig. 1B). A colonoscopic biopsy was conducted for acid-fast bacilli (AFB) smear, Mycobacterium culture, and a PCR test for TB. The AFB smear and TB PCR test results were negative, but 8 weeks after the follow-up colonoscopy, the Mycobacterium culture was positive. The first-line anti-TB drugs were continued, and a follow-up colonoscopy was re-implemented for an endoscopic response assessment 25 weeks after the initiation of the anti-TB drugs. Transverse ulcerations were still observed without significant changes in the ascending colon (Fig. 1C).

The Mycobacterium tuberculosis drug susceptibility test results reported 26 weeks after the initiation of treatment revealed MDR ITB that was resistant to both isoniazid and rifampin. Treatment for MDR ITB was initiated with a combination of pyrazinamide 1.5 g/day, cycloserine 250 mg/day, moxifloxacin 400 mg/day, prothionamide 250 mg/day, p-aminosalicylic acid 3.3 g/day, and streptomycin 750 mg/day. Her constipation was relieved within weeks of the commencement of treatment for MDR ITB. A follow-up colonoscopy was performed 28 weeks from the initiation of treatment for MDR ITB, and showed only scar change in the ascending colon (Fig. 1D). The treatment continued for 24 months and she was declared completely cured.

Discussion

ITB and CD are chronic granulomatous diseases that affect the gastrointestinal tract. Since they share similar clinical features and endoscopic findings, differentiating between them remains challenging. As the incidence of inflammatory bowel disease, including CD, is rapidly increasing in Asian countries [4,5], where the prevalence of TB is relatively high, distinguishing ITB from CD is becoming a more crucial issue in Asia. The clinical significance of differentiating between ITB and CD is relatively low in Western countries because ITB is very rare in this area. However, since ITB can develop in immigrants or immunocompromised patients such as those with HIV/AIDS, western physicians should be aware of the issue.

The two diseases require different treatments. Patients with ITB should receive at least 6 months of anti-TB therapy [6], whereas those with CD should receive anti-inflammatory drugs, immunosuppressants, or biologic agents for life [7]. When a confirmative diagnosis is delayed, the treatment failure or chronic complication rates may increase. Although there are several differences in clinical, endoscopic, histologic, radiologic, and serologic findings between ITB and CD, the only certain ways to diagnose ITB are to identify a caseating granuloma on colonoscopic biopsy, confirm a positive AFB smear, or achieve a positive Mycobacterium culture. However, the exclusive features of ITB are observed in limited patients only [2]. To overcome this limitation, diagnostic prediction models by colonoscopic findings were developed, or an interferon-gamma release assay test was used to make the differential diagnosis between ITB and CD [8910-11]. However, this test can provide false-negative results and its performance can be decreased by other medications such as immunosuppressants [12]. Despite these diagnostic efforts, in cases in which it is difficult to distinguish ITB from CD, it is considered appropriate to administer empirical anti-TB drugs and evaluate the clinical/endoscopic response in 2 to 3 months [13]. In this way, a differential diagnosis between ITB and CD involves a tough decision-making process.

The emergence of drug-resistant ITB may complicate distinguishing ITB from CD. According to a Korean study of the drug resistance patterns of ITB, 17.6% of patients with ITB displayed resistance to at least one anti-TB drug and 2.7% had MDR ITB [2]. If no response is seen to the empirical administration of the first-line anti-TB drugs, the diagnosis of CD is usually made, but the possibility of MDR ITB remains. Thus, one should not exclude the possibility of MDR ITB, even when the diagnosis of CD is most likely based on no response to the empirical first-line anti-TB therapy. Unfortunately, cases of ITB misdiagnosed as CD have been increasing [14]. Therefore, clinicians must become acquainted with the differences between ITB and CD, and when ITB is suspected, Mycobacterium culture of colonoscopic biopsy specimens should routinely be conducted [15].

In summary, differentiating between ITB and CD remains challenging for physicians and may be more complicated by the emergence of MDR ITB. Therefore, for gastroenterologists, it is necessary to figure out the differences between the two diseases. If ITB is suspected, Mycobacterium culture of biopsy specimens should be routinely conducted to prevent a diagnostic delay.

Notes

Conflict of Interest Statement

Suk-Kyun Yang received a research grant from Janssen Korea, which had no role in the design or practice of this study. The other authors disclose no conflicts.

REFERENCES

1.

Ham NS, Myung SJ. 2021; Endoscopic molecular imaging in inflammatory bowel disease. Intest Res 19:33-44

2.

Ye BD, Yang SK, Kim D, Shim TS, Kim SH, Kim MN, et al. 2012; Diagnostic sensitivity of culture and drug resistance patterns in Korean patients with intestinal tuberculosis. Int J Tuberc Lung Dis 16:799-804

3.

Samant H, Desai D, Abraham P, Joshi A, Gupta T, Rodrigues C, et al. 2014; Acid-fast bacilli culture positivity and drug resistance in abdominal tuberculosis in Mumbai, India. Indian J Gastroenterol 33:414-419

4.

Park SH, Kim YJ, Rhee KH, Kim YH, Hong SN, Kim KH, et al. 2019; A 30-year trend analysis in the epidemiology of inflammatory bowel disease in the Songpa-Kangdong district of Seoul, Korea in 1986-2015. J Crohns Colitis 13:1410-1417

5.

GBD 2017 Inflammatory Bowel Disease Collaborators 2020; The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 5:17-30

6.

Park SH, Yang SK, Yang DH, Kim KJ, Yoon SM, Choe JW, et al. 2009; Prospective randomized trial of six-month versus nine-month therapy for intestinal tuberculosis. Antimicrob Agents Chemother 53:4167-4171

7.

Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al. 2019; Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia. Intest Res 17:285-310

8.

Lee YJ, Yang SK, Byeon JS, Myung SJ, Chang HS, Hong SS, et al. 2006; Analysis of colonoscopic findings in the differential diagnosis between intestinal tuberculosis and Crohn's disease. Endoscopy 38:592-597

9.

Kim BJ, Choi YS, Jang BI, Park YS, Kim WH, Kim YS, et al. 2011; Prospective evaluation of the clinical utility of interferon-γ assay in the differential diagnosis of intestinal tuberculosis and Crohn's disease. Inflamm Bowel Dis 17:1308-1313

10.

Bae JH, Park SH, Ye BD, Kim SO, Cho YK, Youn EJ, et al. 2017; Development and validation of a novel prediction model for differential diagnosis between Crohn's disease and intestinal tuberculosis. Inflamm Bowel Dis 23:1614-1623

11.

Limsrivilai J, Pausawasdi N. 2021; Intestinal tuberculosis or Crohn's disease: a review of the diagnostic models designed to differentiate between these two gastrointestinal diseases. Intest Res 19:21-32

12.

Alrajhi S, Germain P, Martel M, Lakatos P, Bessissow T, Al-Taweel T, et al. 2020; Concordance between tuberculin skin test and interferon-gamma release assay for latent tuberculosis screening in inflammatory bowel disease. Intest Res 18:306-314

13.

Ooi CJ, Makharia GK, Hilmi I, Gibson PR, Fock KM, Ahuja V, et al. 2016; Asia Pacific Consensus Statements on Crohn's disease. Part 1: Definition, diagnosis, and epidemiology: (Asia Pacific Crohn's Disease Consensus--Part 1). J Gastroenterol Hepatol 31:45-55

14.

Seo H, Lee S, So H, Kim D, Kim SO, Soh JS, et al. 2017; Temporal trends in the misdiagnosis rates between Crohn's disease and intestinal tuberculosis. World J Gastroenterol 23:6306-6314

15.

Lee YJ, Yang SK, Myung SJ, Byeon JS, Park IG, Kim JS, et al. 2004; The usefulness of colonoscopic biopsy in the diagnosis of intestinal tuberculosis and pattern of concomitant extra-intestinal tuberculosis. Korean J Gastroenterol 44:153-159
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Fig. 1. Serial colonoscopy findings. (A) Initial colonoscopy performed in another hospital reveals multiple transverse ulcers in the ascending colon. (B) Follow-up colonoscopy performed 11 weeks after commencement of the first anti-tuberculosis therapy still shows multiple transverse ulcers in the ascending colon. (C) Follow-up colonoscopy performed 25 weeks after commencement of the first anti-tuberculosis therapy still shows multiple transverse ulcers in the ascending colon. (D) Follow-up colonoscopy performed 28 weeks after therapy for multidrug-resistant intestinal tuberculosis shows only scarring and no active ulcers. A written informed consent for publication and use of medical data and images was obtained from the patient.
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