在微生物学成功的抗结核治疗期间可能发生矛盾的炎症反应。最佳治疗是未知的,但皮质类固醇是最常用的。白细胞介素-1(IL-1)可能在这些矛盾反应的发展中起着核心作用,如果皮质类固醇由于不良反应而失败或不受欢迎,因此,抗IL-1治疗可能是一个合理的选择.
我们展示了7名HIV阴性结核病患者的矛盾反应,两个患有肺外结核,五个患有肺外结核。所有人都接受了皮质类固醇,效果不满意。患者接受IL-1受体拮抗剂anakinra治疗,并监测发热和炎症标志物的减少,病变稳定或消退的影像学证据,和呼吸改善。
在开始抗结核治疗时,6例患者出现贫血,4例患者出现淋巴细胞减少。在矛盾反应的时刻,六名患者出现发烧。Anakinra导致发烧在几天内减少,5例患者的症状缓解和放射学改善。阿纳金拉诱导的中性粒细胞减少症,必须在两名患者中停止治疗,后来很快康复了。
当类固醇失效或不需要时,在HIV阴性结核病患者中可以考虑使用Anakinra。鉴于其良好的安全性和可逆的副作用,可以想象,anakinra也可以用作矛盾反应的一线辅助治疗。
A.v.L.和R.v.C.由美国国立卫生研究院(R01AI145781)支持。
Paradoxical inflammatory responses can occur during microbiologically successful antituberculous therapy. Optimal treatment is unknown, but corticosteroids are used most often. It is likely that interleukin-1 (IL-1) plays a central role in the development of these paradoxical responses, and if corticosteroids fail or are undesirable because of adverse effects, anti-IL-1 therapy may therefore be a rational choice.
We present seven HIV-negative tuberculosis patients with paradoxical responses, two with exclusively pulmonary and five with extrapulmonary tuberculosis. All had received corticosteroids, with unsatisfactory effect. Patients were treated with the IL-1 receptor antagonist anakinra and monitored for reduction of fever and inflammatory markers, imaging evidence of stabilization or regression of lesions, and respiratory improvement.
Six patients had anemia and four patients had lymphopenia at the start of the antituberculosis treatment. Fever was present in six patients at the moment of paradoxical response. Anakinra resulted in the decrease of fever within days, followed by resolution of symptoms and radiological improvement in five patients. Anakinra induced neutropenia, necessitating its cessation in two patients, who recovered quickly afterward.
Anakinra can be considered in HIV-negative tuberculosis patients with paradoxical responses when steroids fail or are undesired. Given its favorable safety profile and reversible side effects, it is conceivable that anakinra might also be used as first-line adjuvant treatment for paradoxical responses.
A.v.L. and R.v.C. are supported by National Institutes of Health (R01AI145781).