Understanding Latent Tuberculosis and Rheumatic Conditions
Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), remains a global health issue, with about 2 to 3 billion people infected worldwide. Interestingly, most individuals with TB do not show symptoms; they harbor a condition known as latent tuberculosis infection (LTBI). Those with LTBI may carry the bacteria without symptoms, but they face a lifetime risk of reactivation, leading to active TB, especially under certain conditions.
For patients with rheumatic diseases, the introduction of biological agents, particularly tumor necrosis factor (TNF) inhibitors, has revolutionized treatment. However, this class of drugs—used to treat conditions like Rheumatoid Arthritis (RA)—can increase the risk of LTBI reactivation. TNF is critical in forming granulomas, which help contain TB bacteria. By inhibiting TNF, these drugs may weaken the body’s ability to control the bacteria, increasing the risk of developing active TB.
The Impact of TNF Inhibitors and Other Biologics on TB Reactivation
TNF inhibitors are not the only medications used in rheumatic diseases, but they are particularly associated with an increased risk of TB reactivation. Studies show that patients with RA who are treated with TNF inhibitors have a TB risk up to 30 times greater than the general population. Other biologics targeting different immune pathways, such as IL-6 inhibitors (tocilizumab) or B-cell depleting agents (rituximab), generally have a lower risk of TB reactivation, making them safer options for those at high risk of LTBI reactivation.
Diagnosing LTBI: Tools and Challenges
The two primary tests used to diagnose LTBI are the Tuberculin Skin Test (TST) and the Interferon-Gamma Release Assay (IGRA). Each has advantages and limitations. TST, widely available and cost-effective, may produce false positives, especially in those vaccinated with the Bacille Calmette-Guérin (BCG) vaccine, common in many countries. IGRA, while more specific and less affected by BCG vaccination, is costly and requires specialized equipment.
Screening Recommendations for LTBI in Rheumatic Patients
Given the high risk of TB reactivation in patients treated with TNF inhibitors, screening for LTBI is essential before initiating these therapies. Recommendations vary by country but generally include a TST or IGRA test, followed by a chest X-ray to rule out active TB in patients who test positive. Annual screening is often recommended for patients who may have ongoing exposure to TB.
Treatment Strategies for LTBI
Treatment for LTBI typically involves either isoniazid (INH) or rifampicin (RMP), depending on the patient’s specific needs and potential drug interactions. INH, taken for six to nine months, remains the first-line treatment. Alternatives like a shorter, four-month RMP regimen are available for those who may struggle with long-term adherence.
Ongoing Research and the Path Forward
Despite progress in screening and treatment, challenges remain, including the need for better diagnostic tests and shorter, more tolerable treatment regimens. Additionally, understanding how to best monitor and support patients with rheumatic diseases who are at risk of TB reactivation remains an area for future research. By continuing to investigate these complexities, healthcare providers can better support patients in managing both their rheumatic conditions and the risks associated with TB.
References https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733747/