American Journal of Gastroenterology
CASE: Biologic therapy has revolutionized the treatment of inflammatory bowel disease (IBD). Nevertheless, it is well known that biologics are associated with an increased risk of opportunistic infections such as tuberculosis (TB). Screening tests indicated before biologic initiation, namely interferon gamma release assay (IGRA) or tuberculin skin tests (TST), may be falsely negative. We present the case of a male with uncontrolled Crohn’s disease (CD) with a negative screen for TB and how a high index of suspicion led to the discovery of latent tuberculosis infection (LTBI) and the appropriate deferment of biologic therapy. A 63-year-old South Asian male with coronary artery disease status post bypass graft, prostate cancer, diabetes and iron deficiency anemia presented with fatigue and dizziness for one week. He reported dark stools since immigration from Bangladesh two years ago. Vital signs and examination were unremarkable. Laboratory studies revealed a gradual decline in hemoglobin from 9 g/dL to 7 g/dL over several months. Esophagogastroduodenoscopy was unremarkable. Colonoscopy revealed friability, inflammation and erythema of the ileocecal valve and terminal ileum (TI) with minimal strictures. Biopsy was consistent with CD. He was started on azathioprine. Subsequent computed tomography (CT) enterography revealed thickened TI extending over a length of 9-10 centimeters. Due to disease severity and continued symptoms, he was referred to our tertiary care center where it was determined that he may benefit from biologic therapy. Patient underwent IGRA testing which was negative. Given his immigration from an endemic area and use of immunosuppressants, a CT of the chest was obtained which was significant for tree-in-bud opacities within the right upper lobe and multiple nodules. Transbronchial biopsy of the largest nodule showed necrotizing granulomatous inflammation. Bronchoalveolar lavage culture was positive for Mycobacterium tuberculosis. The patient was diagnosed with LTBI. Anti-tuberculin therapy was initiated, and biologic therapy was postponed. Biologic agents are increasingly utilized in the treatment of IBD. These agents confer an increased risk of infections i.e. TB and poor outcomes from severe disease. Patients with IBD are also susceptible to infections due to the immunosuppression imposed by the disease itself. The risk of TB varies with the biologic used with the highest relative risks associated with adalimumab and infliximab. Screening for LTBI is indicated in all patients for which biologics are being considered. The goal is to identify and treat individuals at high risk for TB reactivation. A thorough history and examination should be performed to assess pertinent signs and symptoms. While IGRA has demonstrated higher sensitivity and specificity compared to TST, immunosuppressed patients may have a false negative result as in our case. Combination testing may be the most sensitive approach though evidence is limited. In cases of high suspicion, imaging with plain radiograph or CT scan is a useful tool in supporting the diagnosis of LTBI and may show predominantly upper lobe cavitary disease. Biologic therapy for IBD should be deferred until at least one month of treatment for LTBI has been completed.
Masood M, Wasserman R, Nagesh V, Sifuentes H. Latent Tuberculosis Infection In A Patient With A Negative Interferon Gamma Release Assay Prior to Biologic Initiation for Crohn's Disease. American Journal of Gastroenterology. 2021; 116. doi: 10.14309/01.ajg.0000798760.44348.35.