In the tuberculin skin test (TST), a substance called purified protein derivative (PPD), which is derived from tuberculin, is injected under the skin. Typically, PPD produces a T-cell-mediated delayed-type hypersensitivity reaction if the person has been infected with M. tuberculosis. This should produce a wheal reaction. The reaction to the TST should be assessed 48–72 h after the injection. The TST is read by palpating the site of injection to find an area of induration (firm swelling); the diameter of the indurated area should be measured across the forearm. Erythema (redness) should not be measured [35]. The traditional cut-off is 10 mm. The sensitivity is near 100% in immunocompetent patients infected with M.tuberculosis. However, there is a possibility of false-positive testing by cross-reactivity of PPD antigens present in the Mycobacterium bovis strain used for BCG vaccination and in non-tuberculosis mycobacteria (NTM). Sensitivity can also be reduced in patients with other infections, malnutrition, lymphoma, or other immunocompromised conditions. The actual cut-off value that constitutes a positive TST remains controversial due to the cross-reactivity of PPD antigens present in the Mycobacterium bovis strain used for BCG vaccination and in NTM [35].

The use of TST as a diagnostic tool in patients with ileo-colonic inflammation has limitations. Cross-reactivity with BCG, a high prevalence of environmental mycobacteria, and widespread latent M. tuberculosis infection makes interpretation of a positive TST difficult. Anergy in HIV, primary TB, and disseminated TB limits the diagnostic utility of this test. Anergy has also been demonstrated in untreated patients with Crohn’s disease [37]. A prospective evaluation of the differential diagnosis between intestinal TB and Crohn’s disease using a cut-off value of 10 mm achieves 68% sensitivity, 84% specificity, 81% positive predictive value, and 72% negative predictive value [38].

Interferon-gamma release assays (IGRAs) detect the presence of M. tuberculosis infection by measuring the immune response to TB proteins in whole blood. IGRAs offer the possibility of detecting M. tuberculosis infection with greater specificity than TST as M. tuberculosis antigens used in IGRA don’t cross-react with BCG and NTM. IGRAs do not boost subsequent test results and can be completed following a single patient visit. Laboratory tests are not affected by the perceptions or biases of health-care workers in contrast to TST, but results can be dependent on the batching and transport of specimens.

A positive reaction to IGRA also cannot differentiate a latent TB infection (LTBI) from an active TB infection such as TST. Further, a negative reaction to IGRA does not exclude the diagnosis of LTBI or TB disease, and negative predictive value decreases when TB is clinically suspected. As in TST, clinicians should be cautious in interpreting test results in patients with HIV or those who are taking immunosuppressive drugs. A prospective evaluation of the differential diagnosis between intestinal TB and Crohn’s disease using a IGRA shows 67% sensitivity, 90% specificity, 87% positive predictive value, and 73% negative predictive value [38].

Definitive intestinal TB can be diagnosed based on the finding of acid-fast bacilli, caseating granulomas, or M. tuberculosis in culture. A diagnosis of probable intestinal TB is justified in a patient with appropriate clinical manifestations and gross endoscopic findings and evidence of a response to anti-TB treatment (Fig. 10.6) [1, 39]. Although the follow-up period has not been determined, follow-up colonoscopy exams should be performed within 2 to 3 months after initiating anti-TB treatment. If follow-up colonoscopy reveals significant resolution, anti-TB treatment should be maintained for 6 months to treat pulmonary TB [40–42]. After 1 month of treatment, CRP usually recedes to a normal level [19, 43].

In patients who failed to respond to primary anti-TB therapy, the rare possibility of drug-resistant TB must be considered [15, 44, 45]. However, in the absence of acid-fast bacilli, caseating granulomas, or M. tuberculosis in culture, it is difficult to determine which drug-resistant TB is present. In patients who fail to improve after empirical therapy, delayed response to anti-TB treatment may be considered, although this is rare [40]. It is practically difficult to decide to continue anti-TB treatment in cases for which the diagnosis of intestinal TB is not definite and colonoscopy findings fail to show response to anti-TB therapy. Anti-TB response should be interpreted with caution in patients with Crohn’s disease. In some Crohn’s disease patients, anti-TB chemotherapy might be effective in improving particular symptoms, laboratory findings, or colonoscopy findings although it is incomplete or temporary [19, 42]. In cases that lack a treatment response, clinicians should consider other diagnoses, including Crohn’s disease.

TB remains an unresolved infectious disease throughout the world. Differentiating between intestinal TB and Crohn’s disease is a major diagnostic challenge. This is particularly true in Asian countries, which show increasing incidence of inflammatory bowel disease, such as Crohn’s disease. Definite diagnosis of intestinal TB is often difficult to achieve with histological or microbiological proof alone; thus, understanding the endoscopic features is potentially important for differentiating intestinal TB from Crohn’s disease.