TB or CD?TB or CD?

A Aljebreen, MD, Assistant A Aljebreen, MD, Assistant Professor, department of Professor, department of

Medicine, KKUHMedicine, KKUH

Colrectum Forum Colrectum Forum 20072007

Overview Overview

TB and CD epidemiologyTB and CD epidemiology How to diagnose?How to diagnose?

Introduction Introduction In geographical regions where both intestinal

tuberculosis (TB) and Crohn’s disease (CD) coexist, the differential diagnosis of these two conditions poses a challenge to clinicians.

The ultimate course of these two disorders is different.

Intestinal TB is entirely curable, provided that the diagnosis is made early enough and appropriate treatment is instituted.

In contrast, CD is a progressive relapsing illness.

Unfortunately, it is difficult to differentiate intestinal TB from CD because of similar clinical, pathological, radiological, and endoscopic findings.

EpidemiologyEpidemiology of TB of TB

Annual incidence rates of Annual incidence rates of extrapulmonary tuberculosis have been extrapulmonary tuberculosis have been increasing to 4.7 cases per 100,000 increasing to 4.7 cases per 100,000 population in 1997 in Saudi Arabia.population in 1997 in Saudi Arabia.

Extrapulmonary TB represented 28.2% Extrapulmonary TB represented 28.2% of all reported TB cases.of all reported TB cases.

Abdominal TB accounted for 16% of all Abdominal TB accounted for 16% of all extrapulmonary TB in 2 large series extrapulmonary TB in 2 large series from Riyadh and Jeddah. from Riyadh and Jeddah.

Ministry of Health. Tuberculosis. Annual Health Report, 1997. p. 46-49.

EpidemiologyEpidemiology of TB of TB

Gastrointestinal TB was the 2nd Gastrointestinal TB was the 2nd most common type of TB after most common type of TB after pulmonary disease among 820 pulmonary disease among 820 patients with TB between 1982 and patients with TB between 1982 and 1990 (small bowel involvement in 1990 (small bowel involvement in 34% of them)34% of them)

Al-Karawi. J Clin Gastroenterol 1995; 20: 225-232.

CD in Saudi ArabiaCD in Saudi Arabia Very scarce dataVery scarce data It was considered an area “without IBD”It was considered an area “without IBD” 1982, the first 2 cases reported.1982, the first 2 cases reported. In 2003, Al-Ghamdi reported the first study

about CD where they collected 77 cases from 1983-2002.

Concluded there was a definite increase in the incidence of CD

At KKUH we have collected 79 new IBD cases within the last 2 years

So, there is a definite surge of IBDSo, there is a definite surge of IBDAl-Ghamdi et al, WJG Al-Ghamdi et al, WJG 20032003

Extrapulmonary TB: Extrapulmonary TB: difficult to diagnose??difficult to diagnose??

Several forms of extrapulmonary TB Several forms of extrapulmonary TB lack any of the localizing symptoms lack any of the localizing symptoms or signs. or signs.

Cutaneous anergy to PPD was noted Cutaneous anergy to PPD was noted in 35-50% of patients.in 35-50% of patients.

No clinical or radiological evidence No clinical or radiological evidence of pulmonary TB could be found in of pulmonary TB could be found in up to one 3rd of these patients.up to one 3rd of these patients.

Diagnosis: intestinal TB Diagnosis: intestinal TB or CDor CD

They can present exactly with same They can present exactly with same clinical pictures (same age group, clinical pictures (same age group, symptoms and signs)symptoms and signs)

Same radiological findings and same Same radiological findings and same endoscopic findingsendoscopic findings

Mostly with same pathological Mostly with same pathological findingsfindings

So how can we make the diagnosis?So how can we make the diagnosis?

? Other features? Other features

History of previous TBHistory of previous TB CXR findings of TBCXR findings of TB The tuberculin skin test is less The tuberculin skin test is less

helpful, because a positive test does helpful, because a positive test does not necessarily mean active disease.not necessarily mean active disease.

Perianal fistulae and extraintesitnal Perianal fistulae and extraintesitnal manifestations of CDmanifestations of CD

If all negative: any other clues??If all negative: any other clues??

Multiple attempts!!Multiple attempts!!

Endoscopic findings?Endoscopic findings? Laproscopic findings?Laproscopic findings? Histological findings?Histological findings? PCR?PCR? Empirical TB?Empirical TB?

Endoscopic diagnosis?Endoscopic diagnosis? CD (4 parameters)CD (4 parameters)

Anorectal lesions, Anorectal lesions, longitudinal ulcers, longitudinal ulcers, aphthous ulcers, and aphthous ulcers, and cobblestone appearancecobblestone appearance

Intestinal TB (4 parameters)Intestinal TB (4 parameters) involvement of fewer than four segments, involvement of fewer than four segments, a patulous ileocecal valve, a patulous ileocecal valve, transverse ulcers, and transverse ulcers, and scars or pseudopolypsscars or pseudopolyps

Endoscopy. 2006 Jun;38(6):592-7.

Endoscopic diagnosis?Endoscopic diagnosis?

Lee et al hypothesized that a diagnosis of Lee et al hypothesized that a diagnosis of Crohn's disease could be made when the Crohn's disease could be made when the number of parameters characteristic of Crohn's number of parameters characteristic of Crohn's disease was higher than the number of disease was higher than the number of parameters characteristic of intestinal parameters characteristic of intestinal tuberculosis, and vice versa.tuberculosis, and vice versa.

Making these assumptions, the diagnosis of Making these assumptions, the diagnosis of either intestinal tuberculosis or Crohn's disease either intestinal tuberculosis or Crohn's disease would have been made made correctly in 77 of would have been made made correctly in 77 of our 88 patients (87.5 %), incorrectly in seven our 88 patients (87.5 %), incorrectly in seven patients (8.0 %), and would not have been made patients (8.0 %), and would not have been made in four patients (4.5 %). in four patients (4.5 %).

Endoscopy. 2006 Jun;38(6):592-7.

Endoscopic findings: TBEndoscopic findings: TB

In tuberculosis patients, transverse ulcers with surrounding hypertrophic mucosa and multiple erosions were usual colonoscopic findings.

Am J Gastroenterol 1998;93: 606–609.Gastrointest Endosc 2004;59:362-8.

Typical transverse ulcerTypical transverse ulcer

Gastrointest Endosc 2004;59:362-8.

RadiologyRadiology

SBFT reveals a thickened bowel wall with SBFT reveals a thickened bowel wall with distortion of the mucosal folds and distortion of the mucosal folds and ulcerations.ulcerations.

CT may show preferential thickening of the CT may show preferential thickening of the ileocecal valve and medial wall of the cecum ileocecal valve and medial wall of the cecum and massive lymphadenopathy with central and massive lymphadenopathy with central necrosis.necrosis.

Calcified mesenteric lymph nodes and an Calcified mesenteric lymph nodes and an abnormal chest film are other findings that abnormal chest film are other findings that aid in the diagnosis of aid in the diagnosis of intestinalintestinal tuberculosistuberculosis..

At surgery: TBAt surgery: TB Reduced largely since introduction of Reduced largely since introduction of

colonoscopycolonoscopy Indications:Indications:

Mass lesions associated with the hypertrophic form, Mass lesions associated with the hypertrophic form, because they can lead to luminal compromise with because they can lead to luminal compromise with complete obstruction. complete obstruction.

Surgery also may be necessary when free Surgery also may be necessary when free perforation, confined perforation with abscess perforation, confined perforation with abscess formation, or massive hemorrhage occur. formation, or massive hemorrhage occur.

Findings:Findings: The bowel wall appears thickened with an The bowel wall appears thickened with an

inflammatory mass surrounding the ileocecal region. inflammatory mass surrounding the ileocecal region. The serosal surface is covered with multiple The serosal surface is covered with multiple

tubercles. tubercles. The mesenteric lymph nodes frequently are The mesenteric lymph nodes frequently are

enlarged and thickened.enlarged and thickened.

HistologicallyHistologically Intestinal TB: granulomas are

Large, multiple, confluent with caseation Ulcers lined by epitheliod histiocytesUlcers lined by epitheliod histiocytes

CD Fissuring ulcer, lymphoid aggregates, transmural inflammation, and Infrequent, small, noncaseating

granulomas.Am J Gastroenterol

2002;97:1446 –1451.Pulimood et al. Gut 1999

Multiple confluent granulomas, one of which exhibits necrosis.

There is almost no infiltration of neutrophils.

PCR: rapid and accurate?PCR: rapid and accurate?

The positivity rate by PCR in 39 intestinal tuberculosis specimens was 64.1% (25/39), but was zero by PCR in 30 Crohn’s disease specimens.

Moreover, in the tissues of intestinal tuberculosis with granulomas similar to those of Crohn’s disease, there were 71.4% (10/14) positive by PCR, and there were 61.1% (11/18) positive in intestinal tuberculosis tissues without granulomas.

Am J Gastroenterol 2002;97:1446 –1451.

Empirical anti-TBEmpirical anti-TB

If intestinal TB still possibility, give If intestinal TB still possibility, give 4-6 weeks of anti-TB4-6 weeks of anti-TB

30% of CD patietns at China 30% of CD patietns at China receives anti-TB before final receives anti-TB before final diagnosisdiagnosis

? Saudi? Saudi

ASCA?ASCA?

ASCA (IgG and IgA) does not ASCA (IgG and IgA) does not differentiate between CD and differentiate between CD and intestinal TBintestinal TB

No correlation between ASCA and No correlation between ASCA and duration, location and behaviour of duration, location and behaviour of CD and intestinal TBCD and intestinal TB

Makhania et al. Digestive disease & Science. Jan 2007

Microbiology Microbiology

Finding Acid-fast bacilli in one third Finding Acid-fast bacilli in one third of patients. of patients.

The organism also can be recovered The organism also can be recovered in a culture of the involved tissues in a culture of the involved tissues (up to 50% of pts but need 8 weeks)(up to 50% of pts but need 8 weeks)

Horvath et al, AJG 1998

Intestinal TB: when to Intestinal TB: when to call?call?

The The definitivedefinitive diagnosis of diagnosis of intestinalintestinal tuberculosistuberculosis is made by is made by identification of the organism in tissue, identification of the organism in tissue,

either by direct visualization with an either by direct visualization with an acid-fast stain, acid-fast stain,

by culture of the excised tissue, or by culture of the excised tissue, or by a PCR assay.by a PCR assay.

PresumptivePresumptive diagnosis diagnosis

can be established in can be established in A patient with active pulmonary A patient with active pulmonary

tuberculosistuberculosis and radiologic and and radiologic and clinical findings that suggest clinical findings that suggest intestinalintestinal involvement. involvement.

Response to anti-TBResponse to anti-TB

Summary Summary In geographical regions where both intestinal

tuberculosis (TB) and Crohn’s disease (CD) coexist, the differential diagnosis of these two conditions poses a challenge to clinicians.

Unfortunately, it is difficult to differentiate intestinal TB from CD because of similar clinical, pathological, radiological, and endoscopic findings.

Although attempts have been made to distinguish them, there are still no specific differential diagnostic methods up to now.

Polymerase chain reaction (PCR) assay, which allows highly specific and sensitive detection of Mycobacterium tuberculosis has been developed (9 –11), and may provide a novel means for differentiating between these two conditions.