Differentiating Crohn’s disease from tuberculosis

B.S. Ramakrishna

Institute of GastroenterologySRM Institutes for Medical Science

Vadapalani, Chennai 600 026

1932: Crohn’s description 1950: First Indian series

Case History25 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

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

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

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?

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

SEROLOGY/IMMUNOLOGY

Anti-Saccharomyces cerevisiae antibodyAuthor 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%)

TB ELISA

• Meta-analysis of 68 studies– Poor sensitivity

• Sensitivity higher in smear positive patients

– Unreliable specificity• Specificity higher when healthy individuals used for

comparisonSteingart et al. PLoS Med 2007

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

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

RADIOLOGY

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

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

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

ENDOSCOPY

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

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

HISTOPATHOLOGY

HPE of resected specimensTB

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

Mucosal biopsy

Crohn’s versus TB: mucosal biopsies

TB Crohn’s

AFB seen 9% -Caseation 36% -

>4 granulomas/site 45% -Granulomas >400 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

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

MICROBIOLOGY

Confirmation of TB on biopsy

Test % positive AuthorsCaseous 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

TB PCRTB 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

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

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

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

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