Miliary Tuberculosis in a Crohn’s Disease Patient: The Risk beyond the Screening

Abstract

Tumor necrosis factor alpha (TNFα) antagonist is recognized as an effective treatment to achieve clinical remission and healing mucosal in patients with moderate to severe active Crohn’s disease. Considering that it plays a central role in immune-mediated modulation, there are some obvious concerns about its long-term safety. There is evidence that it may increase the risk of opportunistic infections such as tuberculosis, particularly reactivation of previous latent infection. Due to the global high incidence of tuberculosis and its frequent severity in immunocompromised patients, the exclusion of latent infection is currently part of the screening prior to anti-TNFα therapy. Only a few cases of life-threatening disseminated tuberculosis have been reported in immunocompromised patients probably related to widespread use of higher-accuracy screening tests, such as interferon-γ release assays. However, despite negative screening, the risk of active tuberculosis infection remains during treatment. In that instance, tuberculosis infection becomes considerably more difficult to diagnose due to its altered pattern presentation (extrapulmonary and disseminated infection) and is harder to treat because of the high rate of resistance and its associated relevant morbidity and mortality. We report an enigmatic case of a miliary tuberculosis despite negative latent infection screening, using interferon-γ release assays, in a Crohn’s disease patient undergoing treatment with infliximab and azathioprine, focusing on the screening and diagnostic and therapeutic challenge. This case enhances the awareness of anti-TNFα therapy management and the need for strategies to diagnose and treat tuberculosis in this context.

Review article: latent tuberculosis in patients with inflammatory bowel diseases receiving immunosuppression—risks, screening, diagnosis and management

“…Thus, impairing granuloma formation with anti-TNF therapy increases susceptibility to reactivation as well as early dissemination and extra-pulmonary site involvement. [89][90][91] While individual randomised controlled trials did not recognise an increased risk of opportunistic infections with anti-TNFs, subsequent real-world use was associated with an increased incidence of active TB, including miliary TB, across North America and Europe. 85,92,93 An increased risk of opportunistic infections, including TB, associated with anti-TNF therapy was demonstrated in large observational cohorts of patients with rheumatoid arthritis, including in countries with low TB prevalence.…”

“…The presence of TNF‐alpha within macrophage‐rich granulomas confers immunological and physical constraints on the M. tuberculosis infection. Thus, impairing granuloma formation with anti‐TNF therapy increases susceptibility to reactivation as well as early dissemination and extra‐pulmonary site involvement 89‐91 …”

Gastrointestinal Tuberculosis Mimicking Crohn’s Disease

“…Most of the overt TB cases are due to reactivation of latent infection, occurring approximately 12 weeks after the initial exposure to infliximab, usually within the first 6 months of therapy. This drug is associated with a 5-fold increased risk of reactivation of TB in the first 52 weeks after initiation of therapy [7]. Although it is standard of care to perform a chest radiograph and an IGRA test before starting immunosuppressive therapy in CD, the sensitivity of these tests for gastrointestinal TB is approximately 25 and 80%, respectively [4].…”