TB Screening Guidelines for Azathioprine Therapy

Introduction to TB Screening

• The European Crohn's and Colitis Organisation states that routine TB screening is not required before starting azathioprine monotherapy 1
• The British Association of Dermatologists notes that reactivation of latent TB has been reported in rare cases, warranting careful patient selection 2, 1

Risk Stratification by Treatment Regimen

• Azathioprine alone does not significantly increase TB reactivation risk compared to placebo 1
• The combination of azathioprine with anti-TNF agents 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

Indications for TB Screening

• TB screening is indicated before azathioprine if planned combination therapy with anti-TNF agents, history of TB exposure, or prolonged stay in TB-endemic areas 3, 1
• Abnormal chest radiograph suggesting prior TB or history of inadequately treated TB also warrant screening 4

Optimal Screening Protocol

• Clinical risk assessment, chest radiograph, and interferon-gamma release assay (IGRA) are components of TB screening 3
• IGRA is preferred over tuberculin skin test due to higher sensitivity in immunosuppressed patients 3, 1
• Tuberculin skin testing has unacceptably high false-negative rates in immunosuppressed patients, with 83% of patients on steroids or immunomodulators showing anergy to TST 3, 4

Management of Positive Screening

• If active TB is detected, do not start azathioprine and refer immediately to a TB specialist for full evaluation and treatment 4
• If latent TB is detected and combination therapy is planned, treat latent TB before starting anti-TNF therapy, with isoniazid 5 mg/kg daily for 9 months as the preferred regimen 5, 1

Special Populations Requiring Screening

• Black Africans aged >15 years and South Asians born outside the UK may require chemoprophylaxis regardless of test results 4

Common Pitfalls to Avoid

• Don't rely on TST in patients already on immunosuppressants - use IGRA instead 3, 4
• Don't delay screening until combination therapy is planned - test before starting azathioprine if future escalation is possible 1