1. TB or not TB
a diagnostic challenge
Samir Haffar M.D.
Assistant Professor of Gastroenterology

2. • Crohn, Ginzburg & Oppenheimer published
in1932 a landmark paper describing features
of what is known today as Crohn’s disease
• For alphabetic priority these authors chose,
Crohn's disease might well have been
“Ginzburg's” or “Oppenheimer's” disease
Burrill Crohn
Crohn's or Ginzburg's or Oppenheimer's disease
Crohn BB, Ginzburg L, Oppenheimer GD: Regional ileitis, a pathological
& clinical entity. JAMA 1932 ; 99 : 1323.

3. Estimated annual incidence of TB in 2006
Global tuberculosis control: surveillance, planning, financing
WHO report 2008

4. Estimated annual incidence of Crohn’s disease
Kipp AM et al. BMC Public Health 2008 ; 8 : 107.

5. Differentiating Crohn’s disease from ITB
 Clinical features
 Laboratory tests
 Endoscopy
 Pathology
 Radiology (Barium enema – CT)
 Laparoscopy

6.  Clinical features

7. Clinical features of ITB & CD
Nonspecific
Favor diagnosis of CD
Younger age
Aphthoid ulceration
Perianal disease
Enteric fistulae
Extraintest manifestations
Almadi MA et al. Am J Gastroenterol 2009; 104 : 1003 – 1012.
Favor diagnosis of ITB
Absence of rectal bleeding
Absence of diarrhea
Long duration of symptoms
High swinging fever >38.5
Ascites (often absent)

8.  Laboratory tests

9. Tuberculin Skin Test (TST)
• In area of high prevalence of active pulmonary TB
Positive test more likely to be true positive
• In area of low prevalence of active pulmonary TB
Positive test more likely to be false positive
• High false-positive rate where BCG vaccine still given
• High false negative rate if anergy: HIV
Disseminated TB
Corticosteroids
Immunosuppressive
Almadi MA et al. Am J Gastroenterol 2009; 104 : 1003 – 1012.

10. IFN- based assays
• Determine magnitude of IFN- release by T-cells on
exposure to Ag specific to M tuberculosis in vitro
• 2 ELISA tests1 QuantiFERON-TB Gold
QuantiFERON-TB Gold in-tube
High TB prevalence: comparable to TST
High TB prevalence: higher sensitivity
• 1 ELISPOT test2 More sensible & specific than TST
1 Lancet 2006 ; 367 : 1328 – 34.
2 Lancet 2004 ; 364 : 2196 – 203.

11. Quantiferon-TB Gold
FDA approved for diagnosis of latent TB
• Advantages: No crossreaction with BCG
No need to return for reading in 48-72 h
Identify false-positive TSTs (high sp)
• Disadvantage: Don’t distinguish active from latent TB
Don’t predict which pts develop active TB
• Most studies performed on pulmonary TB
One report of QFT-G in diagnosis of 2 cases with ITB 1
• Studies of QFT-G in ITB urgently required 2
1 Caputo D et al. Surg Infect (Larchmt) 2008 ; 9 : 407 – 10.
2 Almadi MA et al. Am J Gastroenterol 2009; 104 : 1003 – 1012.

12. Serologic testing for IBD
• pANCA
Perinuclear antineutrophil cytoplasmic autoantibodies
• ASCA
Antibodies to the yeast Saccharomyces cerevisiae
• anti-ompC
Antibodies to outer membrane porin C of EC
• anti-Cbir1
Antibodies to the bacterial flagellin Cbir1
Clin Gastroenterol Hepatol 2007 ; 5 : 545 – 547.

13. IBD Serology 7
• ASCA IgA
• ASCA IgG
• anti-OmpC IgA
• anti- CBir1
• IBD-specific pANCA
(1) autoantibody detection by ELISA
(2) perinuclear pattern detection by IF assay
(3) DNAse sensitivity
Commercially available in July 2006
93% sensitivity & 95% specificity for IBD

14. Serological tests to differentiate ITB from CD
• ANCA & ASCA 1-3
No significant role to differentiate ITB from CD
Should not be relied upon
1 Amarapurkar DN et al. World J Gastroenterol 2008 ; 14 : 741 – 6.
2 Ghoshal UC et al. Postgrad Med 2007 ; 53 : 166 – 70.
3Makharia GK et al. Dig Dis Sci 2007 ; 52 : 33 – 9.
Epstein D. Aliment Pharmacol Ther 2007 ; 25 : 1373 – 1388.
• IBD Serology 7 4
Their usefulness remains to be seen

15. TB PCR
Very promising
• Intestinal biopsy or surgical specimen 1-2
Specificity 95 %
Accuracy 82.6 %
Speed to made diagnosis 3 days
1 Amarapurkar DN et al. J Assoc Physicians India 2004 ; 52 : 863 – 7.
2 Li JY et al. Diagn Mol Pathol 2000 ; 9 : 67 – 74.
3 Balamurugan R et al. J Clin Microbiol 2006 ; 44 : 1884 – 6.
• Fecal samples 3
Sensibility 89% Specificity 100%
PPV 100% NPV 94%

16. TB culture
• Time consuming (3 – 8 weeks)
• Results frequently negative
Accuracy ranging from 25 to 30%
Amarapurkar DN et al. World J Gastroenterol 2008 ; 14 : 741 – 6.

17.  Endoscopy

18. Endoscopic signs of CD & ITB
Lee’s Criteria
Characteristic of CD Characteristic of ITB
• Involvement of < 4 segs
• Patulous ileocecal valve
• Transverse ulcers
• Scars or pseudopolypds
Lee YJ et al. Endoscopy 2006; 38 : 592 – 597.
First prospective study with 44 patients in each group
• Anorectal lesions
• Longitudinal ulcers
• Aphthous ulcers
• Cobblestone appearance

19. Longitudinal ulcer with normal surrounding mucosa
Crohn’s disease
Aliment Pharmacol Ther 2007 ; 25 : 1373 – 1388.

20. Crohn’s disease
Aphthous ulcers in the rectum in a patient with CD
Lee YJ et al. Endoscopy 2006; 38 : 592 – 597.

21. Crohn’s disease
Longitudinal ulcers & cobblestone appearance
in a patient with Crohn’s disease
Lee YJ et al. Endoscopy 2006; 38 : 592 – 597.

22. Circumferentially orientated intestinal TB ulcer
with erythematous surrounding mucosa
Intestinal tuberculosis
Aliment Pharmacol Ther 2007 ; 25 : 1373 – 1388.

23. Intestinal tuberculosis
Transverse ulcer encircling the entire lumen
in a patient with intestinal tuberculosis
Lee YJ et al. Endoscopy 2006; 38 : 592 – 597.

24. Intestinal tuberculosis
– Patulous ileocecal valve
– Scar changes
– Multiple ulcers
Lee YJ et al. Endoscopy 2006; 38 : 592 – 597.

25. Lee’s Criteria
• Score of + 1 assigned to the 4 parameters of CD
• Score of –1 was given to the 4 parameters of ITB
• Mean value of the scores in CD: 1.61
• Mean value of the scores in ITB: –1.95
• PPV for CD 94%
• PPV for ITB 89%
P < 0.001
Lee YJ et al. Endoscopy 2006; 38 : 592 – 597.

26.  Pathology

27. Biopsies
• Multiple biopsies increases the diagnostic yield
Optimal number of biopsy not established (at least 6)
• Biopsies taken from all segments normal & abnormal
• Ulcerated areas sampled from base & edge of ulcers
• Samples routinely sent for culture & PCR for MT

28. Classic pathology in intestinal TB
• Caseating granulomas
• Acid fast bacilli
• Positive TB culture
< 30%

29. Intestinal TB
Intestinal mucosa showing area of caseous necrosis with
epithelioid cell granulomas characteristic of intestinal TB
Nakamura S et al. Ann Clin Microbiol Antimicrob 2008 ; 7 : 16.

30. Intestinal TB
Acid fast bacilli
Solitary acid fast bacilli in Ziehl-Neelsen staining
highlighting how sparse AFBs may be
Aliment Pharmacol Ther 2007 ; 25 : 1373 – 1388.

31. Features encountered more frequently in ITB
Pulimood’s criteria
• Confluent granulomas
• Multiple granulomas in a given biopsy site
• Large granuloma size
• Submucosal granulomas
• Bands of epithelioid histiocytes lining ulcers
• Disproportionate submucosal inflammation
Pulimood AB et al. J Gastroenterol Hepatol 2005 ; 20 : 688 – 96.
Kirsch R. J Clin Pathol 2006 ; 59 : 840 – 844.

32. Confluent granulomas with caseous necrosis (arrows)
Intestinal Tuberculosis
Kirsch R. J Clin Pathol 2006 ; 59 : 840 – 844.

33. Multiple submucocal granulomas (arrows)
Intestinal tuberculosis
Kirsch R. J Clin Pathol 2006 ; 59 : 840 – 844.

34. Aliment Pharmacol Ther 2007 ; 25 : 1373 – 1388.
Intestinal tuberculosis
Intestinal TB with large granuloma

35. Conglomerate band of epithelioid histiocytes in
an area of ulceration (arrows)
Kirsch R. J Clin Pathol 2006 ; 59 : 840 – 844.
Intestinal tuberculosis
H&E, magnification 20 XH&E, magnification 10 X

36. • Single granulomas as the only foci of granulomatous
inflammation
• Architectural distortion distant from granulomatous
inflammation
Features encountered more frequently in CD
Pulimood’s criteria
Pulimood AB et al. J Gastroenterol Hepatol 2005 ; 20 : 688 – 96.
Kirsch R. J Clin Pathol 2006 ; 59 : 840 – 844.

37. Small mucosal granuloma (arrow)
Kirsch R. J Clin Pathol 2006 ; 59 : 840 – 844.
Crohn’s disease

38.  Radiology

39. Barium enema in intestinal TB
Epstein D. Aliment Pharmacol Ther 2007 ; 25 : 1373 – 1388.
Retraction of the cecum out of the pelvis

40. Barium enema in Crohn’ disease
Epstein D. Aliment Pharmacol Ther 2007 ; 25 : 1373 – 1388.
Ileo-cecal ulcers with destroyed cecum
Bladder fistula

41. Crohn’s disease
Aliment Pharmacol Ther 2007 ; 25 : 1373 – 1388.
Small bowel follow through
– Ileal ulcers & narrowing
– Bowel loop separation
– Preservation of cecal pole

42. These radiological signs are non-specific for
either ITB or CD & have been described in
both conditions

43. CT findings to differentiate ITB from CD
ITB Crohn’s disease
Bowel wall
Symmetrical wall thickening
Asymmetrical wall thickening
Mural stratification
< 6 mm
Exophytic mass
Absent
> 6 mm
No exophytic mass
Present
Separation of bowel loops
By lymphadenopathy
By fibrofatty changes
Present
Absent
Absent
Present
Lymphnodes: > 1 cm
Necrotic center
Present
Present
Absent
Absent
Parital peritoneal thickening Present Absent
Ascites Present Absent
Boudiaf M et al. Eur Radiol 1998 ; 8 : 1221 – 3.

44. CT in Crohn’s disease
– Thickened TI & cecum
– Fibrofatty proliferation
– Enlarged LN
Thoeni RF et al. Radiology 2006 ; 240 : 623 – 638.

45. CT in ITB
Sinan T et al. BMC Med Imaging 2002 ; 2 : 3.
Large necrotic lymph nodes with lucent center
seen in para-aortic area in a patient with ITB

46.  Laparoscopy

47. Laparoscpy in the diagnosis of CD & ITB
• Crohn’s disease
Creeping fat associated with transmural inflammation
• Intestinal TB
Fat wrapping described in patients undergoing
laparotomy for TB in India
Rai S, Thomas WM. J Royal Soc Med 2003 ; 96 : 586 – 8.

48. Laparosopy in the diagnosis of CD & ITB
• Helpful in diagnosing peritoneal TB
• Its role is less clear role in ITB
• Indication of laparoscopy when there is an isolated
involvement of area of small bowel where a biopsy
cannot be obtained through conventional techniques
• With availability of single & double-balloon enteroscopy
these areas can be accessible without laparoscopy

49. Single balloon enteroscopy
Enteroscopy Narrow band imaging
Transverse semicircumferential deep ileal ulcer
Confirmed to be intestinal tuberculosis in a 14-year-old boy
Almadi MA et al. Am J Gastroenterol 2009; 104 : 1003 – 1012.

50. Workup for differential diagnosis of CD or ITB
Ileocolonic inflammation
No caseating granulomas or AFB on tissue biopsy
Clinical & endoscopic risk assessment
TST & chest radiography
Suspicion of ITB ITB is unlikely
Treat as CD
CT abdomen/pelvis
Tissue for PCR & culture
ITB confirmed
Treat as ITB
No evidence of TB
Treat as CD

51. Thank You