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TB or not TB: a diagnostic challenge
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
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)
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.
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.
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.
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.
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
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
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
In North America, an increase in the number of cases with TB has been observed since the mid-1980s mainly attributable to immigration, human immunodeficiency virus and the development of multidrug-resistant strains of TB.
The epidemiology of CD has changed over the years with increasing reports of CD affecting the pediatric population as well as adults.The previously noted north-south gradient in CD incidence was found to be less than previously thought in the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD), this was considered to be a reflection of an increase in the incidence of CD in Southern Europe. In a study from Saudi Arabia, the mean annual incidence of CD over two decades changed from 0.32 / 100,000 to 1.66 / 100,000, representing more than a fivefold increase and a similar observation was found in the pediatric population from the same area.
A recent meta-analysis found that the sensitivity of QFT-G was 70 % , whereas the specificity was 99 % among non-BCG-vaccinated patients and 96 % among BCG-vaccinated patients.Pai M , Zwerling A , Menzies D . Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med 2008 ; 149 : 177 – 84 .
ITB: The majority of ITB cases will involve the ileo-caecum with varying degrees of contiguous colon & small bowel involvement.Approximately 5% will present with a pancolitis picture indistinguishable from UC.
In a study, asymmetric thickening of the colonic wall and enlarged necrotic lymph nodes were highly suggestive of ITB. Boudiaf M , Zidi SH , Soyer P et al. Tuberculous colitis mimicking Crohn’s disease: utility of computed tomography in the differentiation . EurRadiol 1998 ; 8 : 1221 – 3.
