Yokode Akiyoshi, Fujiwara Masaki, Terao Toshiki, Sakamoto Shinji, Yamada Yuto, Sato Ryota, Mishima Momoko, Yada Yuji, Matsuoka Ken-Ichi, Takaki Manabu
Department of Neuropsychiatry Okayama University Hospital Okayama Japan.
Department of Hematology and Oncology Okayama University Hospital Okayama Japan.
PCN Rep. 2025 Mar 2;4(1):e70077. doi: 10.1002/pcn5.70077. eCollection 2025 Mar.
Clozapine-induced agranulocytosis (CLIA) is a rare but serious complication. Fever associated with CLIA is typically treated with broad-spectrum antimicrobials, but empiric antifungal therapy is rarely used. While bacterial and viral infections have been reported in CLIA cases, no cases of fungal infections complicated by CLIA have been documented. We report the first case of CLIA complicated by invasive pulmonary aspergillosis (IPA) in a patient with schizophrenia. The diagnosis of IPA was made using serum β-D-glucan, galactomannan antigen tests, and chest computed tomography (CT).
We present a case of a 51-year-old man with schizophrenia who developed CLIA complicated by IPA. The patient, diagnosed with treatment-resistant schizophrenia, was started on clozapine, but 9 months later he presented with fever, cough, leukopenia, and neutropenia. Clozapine was discontinued, and empirical treatments with cefepime and filgrastim were initiated. Serum β-D-glucan and galactomannan antigen tests were positive, and chest CT showed well-circumscribed nodules, leading to a probable diagnosis of IPA. Antifungal therapy was switched from micafungin to voriconazole according to guidelines. His neutropenia and fever improved, and he was re-transferred to a psychiatric hospital.
CLIA can be complicated by fungal infections. When patients with CLIA present with fever, fungal infections, including IPA, should be considered in the differential diagnosis. Serological tests, including β-D-glucan and galactomannan, are useful for the diagnosis of IPA as well as the appropriate use of antifungal agents in patients with CLIA.
氯氮平所致粒细胞缺乏症（CLIA）是一种罕见但严重的并发症。与CLIA相关的发热通常用广谱抗菌药物治疗，但经验性抗真菌治疗很少使用。虽然在CLIA病例中已报告有细菌和病毒感染，但尚无CLIA并发真菌感染的病例记录。我们报告了首例精神分裂症患者发生CLIA并发侵袭性肺曲霉病（IPA）的病例。IPA的诊断采用血清β-D-葡聚糖、半乳甘露聚糖抗原检测和胸部计算机断层扫描（CT）。
我们报告一例51岁男性精神分裂症患者，发生CLIA并发IPA。该患者被诊断为难治性精神分裂症，开始使用氯氮平治疗，但9个月后出现发热、咳嗽、白细胞减少和中性粒细胞减少。停用氯氮平，并开始使用头孢吡肟和非格司亭进行经验性治疗。血清β-D-葡聚糖和半乳甘露聚糖抗原检测呈阳性，胸部CT显示边界清晰的结节，从而可能诊断为IPA。根据指南，抗真菌治疗从米卡芬净改为伏立康唑。他的中性粒细胞减少和发热情况有所改善，随后转回精神病医院。
CLIA可并发真菌感染。当CLIA患者出现发热时，鉴别诊断应考虑包括IPA在内的真菌感染。血清学检测，包括β-D-葡聚糖和半乳甘露聚糖，对于IPA的诊断以及CLIA患者抗真菌药物的合理使用很有用。
