From the Guidelines
Patients receiving TNF inhibitor therapy are at increased risk for developing both sarcoidosis and extrapulmonary tuberculosis as paradoxical adverse effects, and therefore, thorough screening for latent tuberculosis is essential before initiating therapy. For patients starting TNF inhibitors, screening should include tuberculin skin testing or interferon-gamma release assays, chest radiography, and a detailed history of TB exposure 1.
- Key considerations for screening include:
- Clinical examination
- History of prior TB treatment
- Chest radiograph
- Tuberculin test if appropriate
- Prophylactic isoniazid (300mg daily for 9 months or 900mg twice weekly for 9 months) should be given to patients with latent TB before starting TNF inhibitors to prevent reactivation of TB 1.
- For patients who develop sarcoidosis while on TNF inhibitors, the medication should be discontinued and alternative therapies considered, such as methotrexate, hydroxychloroquine, or corticosteroids depending on disease severity 1.
- If extrapulmonary TB develops, the TNF inhibitor should be immediately stopped and standard multi-drug TB treatment initiated (typically isoniazid, rifampin, ethambutol, and pyrazinamide for 2 months, followed by isoniazid and rifampin for 4-7 months depending on the site of infection) 1. These paradoxical reactions occur because TNF plays a crucial role in granuloma formation and maintenance, which helps contain mycobacterial infections and regulate immune responses 1. When TNF is blocked, granuloma integrity can be compromised, leading to TB reactivation or dysregulated immune responses that manifest as sarcoidosis.
- It is also important to note that the risk of TB reactivation is higher with certain TNF inhibitors, such as infliximab, compared to others like etanercept or adalimumab 1.
- Close cooperation between clinicians prescribing anti-TNF-a and specialists in the management of TB is strongly recommended to ensure proper management of these patients 1.
From the Research
Sarcoidosis and Extrapulmonary Tuberculosis after TNF Inhibitor Therapy
- Sarcoidosis is a systemic granulomatous disease that can affect any organ in the body, with extrapulmonary manifestations being a major cause of morbidity 2.
- Treatment of extrapulmonary sarcoidosis often requires consideration of alternative immunosuppressive agents, topical therapy, or therapy that is not specifically directed against the granulomatous inflammation of the disease 2.
- TNF inhibitors, such as infliximab or adalimumab, may be used to treat inflammatory disease that persists on combination treatment with glucocorticoids and a second-line agent 3, 4.
- However, TNF-α inhibitors can also induce the development of sarcoidosis in some patients treated with biologic TNF-α inhibitors for other diseases, highlighting the complexity of the role of TNF-α in granuloma formation 5.
- The differential diagnosis between tuberculosis (TB) and sarcoidosis can be challenging due to their clinical, immunologic, and radiologic similarities, and some cases have been described in which patients have both diseases concomitantly 6.
- In patients with both TB and sarcoidosis, treatment decisions can be complicated by the need to balance immunosuppression for sarcoidosis with the risk of exacerbating TB 6.