Department of Neurology, Nitobe Memorial Nakano General Hospital, 4-59-16 Chuo Nakano-ku, Tokyo, 164-8607, Japan.
Department of Infection Prevention and Control, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
BMC Infect Dis. 2020 Sep 29;20(1):708. doi: 10.1186/s12879-020-05396-7.
Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy.
A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident.
We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.
经尿道膀胱内卡介苗（BCG）给药已被证明可有效治疗和预防浅表膀胱癌和原位癌的复发，并可预防疾病进展。然而，可能会出现致命的副作用，如播散性感染。早期诊断和准确治疗间质性肺炎（IP）非常重要，因为感染引发的 IP 恶化是主要的死亡原因。尽管一些死亡报告提示在膀胱内 BCG 治疗后出现新的 IP，但据我们所知，尚无报告证明现有的 IP 急性恶化。此外，之前的报告中缺乏尸检。我们报告了一例 BCG 灌注后发生致命性 IP 恶化的患者，并展示了尸检的病理学发现。
一名 77 岁男性，有 IP 病史，因发热和不适被转诊至我院。他在入院前 1 天接受了膀胱内 BCG 注射。入院后使用抗结核药物后，他的发热得到缓解，于是出院回家。他在出院后 7 天因高热再次被转至我院。入院时，他表现为高热和全身出疹。还观察到肝脾肿大和骨髓抑制。肝和骨髓活检显示有多个上皮样细胞肉芽肿，伴有朗汉斯巨细胞。骨髓、痰液和血液的牛型分枝杆菌活检 DNA 分析均为阴性。他的氧需求急剧恶化，胸部 CT 扫描显示磨玻璃影扩大。他被诊断为现有 IP 的急性恶化。我们重新开始使用抗结核药物和类固醇脉冲治疗，但他在第 35 天因呼吸衰竭而死亡。尸检显示，多个器官中弥漫性存在多个上皮样细胞肉芽肿，伴有朗汉斯巨细胞，但未发现 BCG。
我们报告了首例由 BCG 感染引起的慢性 IP 急性恶化病例。这也是首例膀胱内 BCG 治疗引起的现有 IP 急性恶化的尸检病例。急性 IP 恶化的诱因是感染还是对 BCG 的过敏反应仍存在争议，因为缺乏病理证据证实 BCG 感染。使用 BCG 治疗膀胱癌的医生应该警惕 IP 的急性恶化。
