Is a tuberculosis (TB) test required before starting azathioprine?

TB Testing Before Azathioprine: Not Routinely Required for Monotherapy

TB screening is not routinely required before starting azathioprine monotherapy, but becomes essential if azathioprine will be combined with anti-TNF agents or in patients with specific TB risk factors. 1

Risk Stratification by Treatment Regimen

Azathioprine Monotherapy (Low Risk)

• Azathioprine alone does not significantly increase TB reactivation risk compared to placebo 1
• The European Crohn's and Colitis Organisation states that routine TB screening is not required before starting azathioprine monotherapy 1
• However, the British Association of Dermatologists notes that reactivation of latent TB has been reported in rare cases, warranting careful patient selection 2, 1

Combination Therapy (High Risk)

• When azathioprine is combined with anti-TNF agents, TB screening becomes mandatory 1
• The combination increases TB reactivation risk 13-fold compared to anti-TNF monotherapy 1
• The American Gastroenterological Association requires TB screening before initiating combination therapy with azathioprine plus anti-TNF agents or JAK inhibitors 1

When TB Screening IS Indicated

Perform TB screening before azathioprine if any of the following apply:

• Planned combination therapy with anti-TNF agents (infliximab, adalimumab, etanercept) 2, 1
• History of TB exposure or household contacts with TB 2
• Prolonged stay or origin from TB-endemic areas 2
• Abnormal chest radiograph suggesting prior TB 2
• History of inadequately treated TB 2

Optimal Screening Protocol (When Indicated)

Components of TB Screening

1. Clinical risk assessment: Document TB exposure history, endemic area residence/travel, prior TB treatment 2
2. Chest radiograph: Mandatory to detect active disease or residual lesions 2
3. Interferon-gamma release assay (IGRA): Preferred over tuberculin skin test 2, 1

Why IGRA Over TST

• Tuberculin skin testing has unacceptably high false-negative rates in immunosuppressed patients 2
• 83% of patients on steroids or immunomodulators (including azathioprine) show anergy to TST 2
• Only 71% of IBD patients responded to any skin antigen testing, with no positive TST results in one study 2
• IGRA maintains better sensitivity, though it is also negatively affected by immunosuppression 1, 3

Critical Timing Consideration

Perform TB screening BEFORE starting any immunosuppressive therapy, not after 1, 3

• Both TST and IGRA sensitivity are significantly reduced once immunosuppressive therapy begins 1, 3
• Patients already on azathioprine had IGRA positive rates of only 11.8% versus 27.3% in treatment-naive patients 3
• This creates a window where latent TB may be missed if screening is delayed 3, 4

Management of Positive Screening

If Active TB Detected

• Do not start azathioprine 2
• Refer immediately to TB specialist for full evaluation and treatment 2

If Latent TB Detected (and combination therapy planned)

• Treat latent TB before starting anti-TNF therapy 1
• Isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months is preferred 2, 1
• Alternative regimens: 6 months isoniazid or 4 months rifampin 2, 1
• Delay biologic therapy for at least 3-4 weeks after starting latent TB treatment 1

Special Populations Requiring Screening

• Black Africans aged >15 years: Consider chemoprophylaxis regardless of test results 2
• South Asians born outside the UK: Consider chemoprophylaxis with 6 months isoniazid 2
• Patients switching from azathioprine to other immunosuppressants: Consider prophylactic anti-TB treatment, as switches have triggered TB reactivation 5

Common Pitfalls to Avoid

• Don't rely on TST in patients already on immunosuppressants - use IGRA instead 2
• Don't delay screening until combination therapy is planned - test before starting azathioprine if future escalation is possible 1, 3
• Don't assume negative screening eliminates all risk - false negatives occur, and primary TB infection can develop during treatment, especially in endemic areas 2, 4
• Don't forget chest radiography - it may reveal residual lesions even when immunologic tests are negative 2, 6