Pavone Paolo, Arletti Laura, Ilariucci Fiorella, Albano Tommaso, Lusetti Deborah, Corsini Romina, Merli Francesco, Mezzadri Sergio
Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Emilia-Romagna, Italy.
J Fungi (Basel). 2024 Aug 17;10(8):584. doi: 10.3390/jof10080584.
Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells/µL), his c-reactive protein was 27 mg/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg/mL (wako method), while serum galactomannan 3.6. BAL was positive for culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists.
在动物模型中，CCR - 4拮抗剂治疗已显示出对侵袭性肺曲霉病的发生具有保护作用。在此，我们报告一例接受莫加莫拉单抗治疗的患者发生致命性侵袭性肺曲霉病的病例。一名64岁患有难治性蕈样霉菌病的男性在2022年6月胸部CT检查时发现双侧弥漫性肺结节。支气管肺泡灌洗（BAL）真菌和细菌培养以及半乳甘露聚糖检测均为阴性，血清β - 葡聚糖和半乳甘露聚糖检测结果也为阴性。组织学检查显示淋巴细胞浸润，真菌染色阴性，因此初步诊断为淋巴瘤浸润，该患者于2022年8月开始接受CCR - 4拮抗剂莫加莫拉单抗治疗。直到11月他前往血液科门诊报告呼吸困难之前，他都没有症状。他出现中性粒细胞增多（18.6×10⁹细胞/µL），C反应蛋白为27 mg/dL，蕈样霉菌病的皮肤病变刚开始有所改善。CT扫描显示双侧弥漫性大的严重坏死空洞性病变，壁增厚，且明显同步进展。β - 葡聚糖为31 pg/mL（和光法），血清半乳甘露聚糖为3.6。BAL培养和半乳甘露聚糖检测呈阳性。患者开始使用伏立康唑治疗，但尽管病情稳定，两天后他突然死亡。讨论：矛盾的是，已有报告称纳武单抗治疗后慢性肺曲霉病会恶化，免疫重建综合征通常在强化化疗后中性粒细胞恢复期间出现。我们的患者在确诊曲霉病前5个月就已存在惰性肺部病变，在确诊前他一直完全无症状，直到曲霉病诊断后很快去世。即使预计病变在5个月内会进展，但该病例表现不典型。在这5个月期间，他没有肺部症状，C反应蛋白检测为阴性。此外，在亚急性/慢性曲霉病的自然进展过程中，预计会出现不同的影像学表现，病情较轻且可能进展不同步。我们认为与莫加莫拉单抗相关的免疫恢复（皮肤病变的同时临床反应也支持这一点）在本病例中可能是有害的，加剧了灾难性的免疫反应，或者掩盖了曲霉病的临床进展。临床医生应意识到免疫重建综合征可能会导致开始使用CCR - 4拮抗剂的免疫受损患者出现致命后果。
