Crohn vs tb 2015 03 22 tnisgcon

1. Differentiating Crohn’s disease
from tuberculosis
B.S. Ramakrishna
Institute of Gastroenterology
SRM Institutes for Medical Science
Vadapalani, Chennai 600 026

2. 1932: Crohn’s description
1950: First Indian series

3. Case History
25 year old unmarried lady with 10 month h/o:
•Episodic abdominal pain
•Episodic vomiting
•Loose stools, 6 per day, small volume, no blood
For the last two months has developed
•Swelling of legs
•Weight loss

4. Case History
On examination
•Height 5 feet 2 inches, Weight 34 kg
•Pallor +, Mild pitting oedema at ankles +
•Abdominal examination – vague resistance in
lower abdomen, no definite mass
•Rectal examination normal

5. Investigations
• Complete blood counts
– Hb 10.2 g/dL, MCV 74 fL
– WBC 8500/cu.mm.
– Platelet count – 320,000/cu.mm.
• ESR: 35 mm/h
• CRP: 9 mg/L
• S. Albumin: 3.2 g/dL

6. Investigations
• Colonoscopy: Ulcers in ileum and caecum.
• Biopsies: Multiple small granulomas in ileum.
Chronic inflammation in caecum. Other sites
showed mild active colitis.
Diagnosis: Crohn’s disease or TB?

7. Clinical features that may help!
TB Crohn’s
Duration of illness <12 months >12 months
Fever Evening fever with
night sweats
No specific pattern
Family history TB Crohn’s
Recurrence of
disease after surgery
Unlikely Yes
Perianal disease Unlikely Often present
Ascites May occur, exudate Uncommon, transudate
Extraintestinal
manifestations
Involvement of lungs,
lymph nodes
Arthropathy, PSC

8. SEROLOGY/IMMUNOLOGY

9. Anti-Saccharomyces cerevisiae antibody
Author TB Crohn’s
Makharia et al, 2007 14/30 30/59
Ghoshal et al, 2007 8/16 10/16
Amarapurkar et al, 2008 11/26 10/26
Dutta et al, 2011 3/30 9/30
TOTAL 36/102
(35.2%)
59/131
(45.0%)

10. TB ELISA
• Meta-analysis of 68 studies
– Poor sensitivity
• Sensitivity higher in smear positive patients
– Unreliable specificity
• Specificity higher when healthy individuals used for
comparison
Steingart et al. PLoS Med 2007

11. Interferon-gamma release assay (IGRA)
• RD1-antigen (recombinant antigen from RD1 region of
MTB) based assays
– Diagnoses latent TB
– Usually positive in active TB, except miliary TB
– May be positive in some patients with untreated
Crohn’s disease

12. Tuberculin (PPD) skin test
• PPD reactivity rate in Crohn’s disease in India
& other TB endemic countries not known
• PPD testing advised by US FDA prior to
infliximab therapy in order to prevent TB
reactivation

13. RADIOLOGY

14. Ileocaecal TB
•Straightening of IC
junction
•Narrow caecum
•Nodules
•Transverse ulcers

15. Crohn’s disease
•Omega sign
•Longitudinal ulcer
•Shortening of mesenteric
border

17. CD versus TB: CECT abdomen
TB Crohn’s
Wall thickening Absent or
asymmetric
Concentric
Target sign Absent Present in 50%
Lymph nodes Central necrosis in
1/3
No central necrosis
Bowel displacement Due to lymph nodes Fibrofatty change
Makanjuola et al, AJR 1998

18. ENDOSCOPY

19. Colonoscopy in TB
• Superficial well defined ulcers with irregular
margins
• Nodular mucosa
• Deformed IC valve with ulcers
• Ileocecal involvement
• Skip lesions in 10%
• Segmental involvement in 26%
• Pancolitis in 4%
Shah S et al, Gut 1992

20. Colonoscopy in Crohn’s disease
• Aphthous ulcers
• Deep irregular ulcers
• Longitudinal ulcers
• Cobblestones
• Pseudopolyps
• Mucosal bridging
• Discontinuous involvement (Skip lesions)
• Luminal narrowing
• Fistulas

23. HISTOPATHOLOGY

24. HPE of resected specimens
TB
159 cases
Crohn’s
10 cases
Miliary nodules on
serosa
Common, conspicuous Rare
Length of strictures <3 cm Usually long
Internal fistulae Uncommon Rare
Perforation Uncommon Rare
Ulcers Circumferential. Usually
transverse.
Mesenteric attachment.
Longitudinal / serpiginous
Lymph nodes Large Small
Granulomas May be present in
mesenteric nodes when
absent in intestine
Not present in nodes when
absent in intestine
Tandon and Prakash, Gut 1972

25. Mucosal biopsy

26. Crohn’s versus TB: mucosal biopsies
TB Crohn’s
AFB seen 9% -
Caseation 36% -
>4 granulomas/site 45% -
Granulomas >400µ 51% -
Confluent granulomas 42% 3%
Band of epithelioid histiocytes 61% -
Single small granulomas 3% 26%
Mucosal changes distant to granulomas - 65%
Pulimood et al, Gut 1999; Pulimood et al, JGH 2004

27. Value of upper GI endoscopy and biopsy
• In 11% of children, the diagnosis of CD was
based entirely on UGI biopsy findings and
granulomas on biopsy
– Focal duodenal cryptitis
– Focally enhanced gastritis
– Sensitivity 99%, specificity 93%
Hummel et al, JPGN 2012

28. MICROBIOLOGY

29. Confirmation of TB on biopsy
Test % positive Authors
Caseous necrosis 23-36% Lee 2004, Pulimood
2005
AFB smear of biopsy 5-10%
AFB culture of biopsy 7-40% Bhargava 1985, Lee
2004, Khan 2006
AFB culture of surgical
tissue
70% Veeragandham 1996

30. TB PCR
TB Crohn’s
Moatter et al 1998 8/12 -
Gan et al 2002 25/39 0/30
Amarapurkar et al 2004 17/26 0/26
Pulimood et al 2008 6/20 1/20
Balamurugan et al 2008 21/26 5/46

31. TB versus Crohn’s
Search for extraintestinal tuberculosis
• Search for peripheral lymphadenopathy 
FNAC, culture, PCR, and biopsy
• Search for pulmonary lesion on chest x-ray, and
do induced sputum for AFB (x3), sputum PCR,
bronchoalveolar lavage if necessary
• Search for ascites, aspirate and send for cells,
protein, culture, PCR

32. Diagnosis of ITB
• Histology + Culture diagnostic in 60%
Bhargava DK et al, 1992
• Histology + Culture + Extra-intestinal TB
diagnostic in 56% of 225 patients Lee et al 2004

33. Diagnosis of ITB
• Histology + Culture diagnostic in 60%
Bhargava DK et al, 1992
• Histology + Culture + Extra-intestinal TB
diagnostic in 56% of 225 patients Lee et al 2004
• Histology + culture diagnostic in 80%; addition
of stool TB PCR diagnosed 100% of 26 ITB
patients Balamurugan et al, 2011

39. Summary
• Differentiating TB from Crohn’s disease is
difficult in a significant number of patients
• Duration & extraintestinal features helpful
• Radiological imaging and colonoscopy helpful
• Segmental biopsies advisable
• Avoid double treatment as far as possible
• Consider laparoscopy and biopsy if diagnosis
uncertain