From the Guidelines
Patients with sarcoidosis who develop extrapulmonary tuberculosis after starting TNF inhibitors should immediately discontinue the TNF inhibitor and begin a standard four-drug anti-tuberculosis regimen consisting of isoniazid (300 mg daily), rifampin (600 mg daily), ethambutol (15-25 mg/kg daily), and pyrazinamide (20-25 mg/kg daily) for 2 months, followed by isoniazid and rifampin for an additional 4-7 months depending on the site and severity of infection. This situation represents a paradoxical complication, as TNF inhibitors like infliximab, adalimumab, or etanercept, while effective for treating sarcoidosis, significantly increase the risk of tuberculosis reactivation by disrupting granuloma integrity, as noted in the British Association of Dermatologists' guidelines 1. Prior to initiating any TNF inhibitor therapy, patients should undergo thorough TB screening including tuberculin skin testing or interferon-gamma release assay, chest radiography, and risk assessment, as recommended by the BTS guidelines 1. For patients with extrapulmonary TB, infectious disease consultation is essential to guide treatment duration and monitoring. After completing TB treatment, if sarcoidosis therapy is still needed, consider non-TNF inhibitor alternatives such as methotrexate, hydroxychloroquine, or corticosteroids. If TNF inhibitor reinitiation is necessary, it should be delayed until TB treatment completion and only with close monitoring. Regular follow-up with both pulmonology and infectious disease specialists is crucial to monitor for treatment response and potential complications.
Some key points to consider in the management of extrapulmonary tuberculosis in patients on TNF inhibitors include:
- The risk of tuberculosis may be greater with monoclonal antibodies (infliximab and adalimumab) as compared with etanercept, with incidences of tuberculosis in patients with RA reported to the BSRBR of 39 per 100,000 patient-years for etanercept, 103 per 100,000 patient-years for infliximab and 171 per 100,000 patient-years for adalimumab 1.
- The clinical presentation of infection is often atypical, with at least 50% of cases associated with infliximab being extrapulmonary, and late diagnosis, development of disseminated disease, and concomitant immunosuppressive therapy may all contribute to high rates of morbidity and associated mortality 1.
- The BTS guidelines recommend that patients with an abnormal chest radiograph or a history of prior pulmonary or extrapulmonary TB not previously adequately treated should have active TB excluded by appropriate investigations under the care of a thoracic or infectious disease physician, and that chemoprophylaxis should be given before commencing anti-TNF-a treatment if the annual risk of TB is greater than the risk of drug-induced hepatitis 1.
From the Research
Extrapulmonary Tuberculosis in Patients After Starting TNF Inhibitors for Sarcoidosis
- There is no direct evidence in the provided studies that specifically addresses the development of extrapulmonary tuberculosis in patients after starting TNF inhibitors for sarcoidosis.
- However, the studies discuss the use of TNF inhibitors in the treatment of sarcoidosis, including extrapulmonary manifestations 2, 3.
- Sarcoidosis is a systemic disease that can affect any organ in the body, and extrapulmonary manifestations are a major cause of morbidity 4, 5.
- The use of anti-TNF-α agents has been shown to be effective in the treatment of refractory sarcoidosis, including extrapulmonary sarcoidosis, with a combined overall treatment success rate of 74.5% 2.
- The management of extrapulmonary sarcoidosis can be challenging, and treatment options may vary depending on the individual patient and the specific organ systems involved 6.
- It is essential to note that the provided studies do not directly address the risk of developing extrapulmonary tuberculosis in patients with sarcoidosis who are treated with TNF inhibitors, and further research would be needed to determine this risk 4, 2, 5, 3, 6.