Zhang Jiaojiao, Luo Jing, Weng Xiangqin, Zhu Yongmei, Goyal Gaurav, Perna Fabiana, Espinoza-Gutarra Manuel, Jiang Lu, Chen Li, Mi Jian-Qing
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Division of Hematology and Oncology, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA.
Ann Transl Med. 2022 Jun;10(12):722. doi: 10.21037/atm-22-2533.
Central nervous system (CNS) mucormycosis is insidious and difficult to diagnose. It progresses rapidly and causes high mortality. Rare cases have been reported during ibrutinib use, which have poor prognosis. Through this case, we share the experience of successful diagnosis and treatment. We also emphasize the importance of focusing on high-risk groups, early diagnosis and prompt management.
In this case, a 52-year-old patient was diagnosed with chronic lymphocytic leukemia (CLL) for more than 5 years. He was in remission after rituximab plus fludarabine and cyclophosphamide (RFC) regimen, and relapsed in the fourth year. During the ibrutinib monotherapy, the patient presented with sudden headache. Cranial imaging examination revealed a definite right occipitoparietal lobe mass with extensive edema. A rapid diagnosis of mucormycosis infection was made using metagenomic next-generation sequencing (mNGS). The patient at that time didn't have neutropenia, but he had hypogammaglobulinemia. The infection was treated with amphotericin B cholesteryl sulfate complex, posaconazole, and interventional surgery, and the treatment was successful. At the same time, we considered the control of disease progression in this relapsed patient with, as well as to the drug interaction with posaconazole. We chose the next generation Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib as the treatment, whose safety has been identified. As of the submission date, the patient has been followed up for nearly 1 year, and his disease is stable.
When new clinical problems arise in recurrent CLL patients, it is important to identify multiple factors, especially the insidious fungal infections. In particular, the immunocompromised patients should be concerned. CNS mucormycosis is extremely deadly, the early diagnosis will improve the prognosis. In clinical practice, the gold standard diagnosis of mucormycosis is difficult to obtain through pathology. In this case, mNGS was applied to quickly diagnose mucormycosis, enabling earlier treatment and ameliorating the prognosis. Thus, it will help us to early detect this group of people who may be potentially infected. Current guidelines do not recommend the prophylactic use of antifungal agents in treated CLL patients. However, in patients with prior severe infection or hypogammaglobulinemia, intravenous immunoglobulin is recommended to reduce the associated infection rate.
中枢神经系统（CNS）毛霉菌病隐匿且难以诊断。其进展迅速，死亡率高。在使用伊布替尼期间报告的罕见病例预后较差。通过本病例，我们分享成功诊断和治疗的经验。我们还强调关注高危人群、早期诊断和及时处理的重要性。
在本病例中，一名52岁患者诊断为慢性淋巴细胞白血病（CLL）已5年多。他在接受利妥昔单抗加氟达拉滨和环磷酰胺（RFC）方案治疗后缓解，并在第4年复发。在接受伊布替尼单药治疗期间，患者突然出现头痛。头颅影像学检查显示右枕顶叶有明确肿块并伴有广泛水肿。通过宏基因组下一代测序（mNGS）快速诊断为毛霉菌感染。患者当时没有中性粒细胞减少，但有低丙种球蛋白血症。感染采用硫酸胆固醇两性霉素B、泊沙康唑及介入手术治疗，治疗成功。同时，我们考虑控制该复发患者的疾病进展以及与泊沙康唑的药物相互作用。我们选择新一代布鲁顿酪氨酸激酶（BTK）抑制剂泽布替尼进行治疗，其安全性已得到确认。截至提交日期，患者已随访近1年，病情稳定。
复发CLL患者出现新的临床问题时，识别多种因素很重要，尤其是隐匿性真菌感染。特别是免疫功能低下患者应予以关注。CNS毛霉菌病极其致命，早期诊断可改善预后。在临床实践中，毛霉菌病的金标准诊断难以通过病理学获得。在本病例中，mNGS用于快速诊断毛霉菌病，实现了更早治疗并改善了预后。因此，这将有助于我们早期发现这组可能潜在感染的人群。目前的指南不建议在接受治疗的CLL患者中预防性使用抗真菌药物。然而，对于既往有严重感染或低丙种球蛋白血症的患者，建议使用静脉注射免疫球蛋白以降低相关感染率。
