Service de pneumologie et réanimation respiratoire, centre de compétence « Maladies rares pulmonaires », hôpital Tenon, Assistance publique-Hôpitaux de Paris (AP-HP), 4, rue de la Chine, 75970 Paris cedex 20, France.
Joint Bone Spine. 2011 Jul;78(4):352-7. doi: 10.1016/j.jbspin.2010.12.001. Epub 2011 Jan 20.
TNF-α antagonist therapy is associated with a risk of severe, extrapulmonary, disseminated tuberculosis, which is fatal in 10% of cases. The risk of tuberculosis is increased four-fold in patients on TNF-α antagonist therapy. The main risk factors are a history of untreated or inadequately treated primary tuberculosis, recent contact with a tuberculosis patient, and residence in or travel to a high-endemicity region. Infection surveillance agencies throughout the world have issued recommendations to ensure the detection and treatment of latent tuberculosis before TNF-α antagonist initiation. These recommendations have returned the incidence of tuberculosis to the level seen before the introduction of TNF-α antagonists. Nevertheless, there is still room for improvement. Recommendations about latent tuberculosis screening include the use of tuberculin skin tests. However, these tests are positive in individuals vaccinated with the BCG vaccine, which leads to overuse of tuberculosis chemoprophylaxis and, therefore, to unnecessary patient exposure to hepatotoxic effects. Furthermore, tuberculin skin tests may be falsely negative in immunosuppressed patients, leading to underuse of tuberculosis prophylaxis. These shortcomings of tuberculin skin tests have generated interest in interferon-gamma release assays (IGRAs). In patients with overt tuberculosis, IGRAs are more sensitive and more specific than tuberculin skin tests. However, the accuracy of IGRAs for diagnosing latent tuberculosis remains unknown, because no reference standard is available. In addition, patients taking immunosuppressant agents to treat systemic disease may exhibit anergia, which complicates the interpretation of IGRAs. Until additional data become available, caution requires that IGRAs be used only when a positive or negative result, as assessed on a case-by-case basis, will help to decide whether tuberculosis chemoprophylaxis is in order.
肿瘤坏死因子-α拮抗剂治疗与严重的肺外、播散性结核相关，其病死率为 10%。TNF-α 拮抗剂治疗患者的结核发病风险增加了 4 倍。主要的危险因素包括未治疗或治疗不充分的原发性结核病史、近期与结核患者接触、居住或旅行至高发地区。全世界的感染监测机构都发布了建议，以确保在开始 TNF-α 拮抗剂治疗之前发现和治疗潜伏性结核。这些建议使结核的发病率恢复到 TNF-α 拮抗剂引入之前的水平。然而，仍有改进的空间。关于潜伏性结核筛查的建议包括使用结核菌素皮肤试验。然而，这些试验在接种卡介苗的个体中呈阳性，这导致了结核化学预防的过度使用，从而使患者不必要地暴露于肝毒性作用之下。此外，结核菌素皮肤试验在免疫抑制患者中可能呈假阴性，导致结核预防不足。这些结核菌素皮肤试验的缺点引起了干扰素-γ释放试验（IGRAs）的兴趣。在显性结核患者中，IGRAs 比结核菌素皮肤试验更敏感和更特异。然而，IGRAs 用于诊断潜伏性结核的准确性仍不清楚，因为没有参考标准。此外，接受免疫抑制剂治疗全身性疾病的患者可能会出现无反应性，这使 IGRAs 的解释变得复杂。在获得更多数据之前，需要谨慎地仅在根据具体情况评估阳性或阴性结果将有助于决定是否需要进行结核化学预防时使用 IGRAs。
