肺毛霉病临床特征分析

Clinical characteristics of pulmonary mucormycosis

目的分析肺毛霉病患者临床资料,探讨肺毛霉病临床特征及诊疗方案。方法2021年1月—2023年4月漯河市中心医院诊治肺毛霉病患者33例,记录临床症状、实验室检查、影像学检查、病原学诊断结果、治疗方案及预后等临床资料。结果33例患者中发热24例,咳嗽33例,咯血18例;基础疾病为糖尿病19例,实体器官移植6例,血液病5例,慢性肾脏病3例,无基础疾病1例;合并病毒感染23例。33例患者C反应蛋白48.1(8.5,108.0)mg/L,红细胞沉降率(57.5±27.9)mm/h,血常规、肝功能、肾功能检查均无异常。33例患者肺部CT影像表现呈多样性,多种征象同时并存,表现为实变26例,空洞16例,气道狭窄15例,胸腔积液13例,纵隔及肺门淋巴结肿大11例,肺磨玻璃影4例,肺结节2例,“反晕征”2例,支气管炎1例;多肺叶受累31例,单肺叶受累2例。宏基因组二代测序诊断肺毛霉病的阳性率(86.7%)高于涂片镜检(24.2%)、真菌培养(15.2%)、组织病理(50.0%)(χ^(2)=24.649,P<0.001;χ^(2)=32.156,P<0.001;χ^(2)=8.314,P=0.004),组织病理高于涂片镜检、真菌培养(χ^(2)=3.873,P=0.049;χ^(2)=7.771,P=0.005),涂片镜检与真菌培养比较差异无统计学意义(χ^(2)=0.862,P=0.353)。33例患者中单纯抗真菌药物治疗25例,其中两性霉素B单药治疗2例,泊沙康唑或艾沙康唑单药治疗6例,两性霉素B联合泊沙康唑或艾沙康唑治疗17例;手术联合抗真菌药物治疗7例,其中术后泊沙康唑单药治疗1例,两性霉素B联合泊沙康唑治疗6例;放弃治疗1例。单药治疗8例中好转出院7例,多药联合治疗17例中好转出院14例;单药治疗有效率(87.5%)与多药联合治疗(82.4%)比较差异无统计学意义(P>0.999)(Fisher确切概率法)。单纯抗真菌药物治疗25例中好转出院21例,死亡4例;手术联合抗真菌药物治疗7例中好转出院6例,死亡1例;单纯抗真菌药物治疗有效率(84.0%)与手术联合抗真菌药物治疗(85.7%)比较差异无统计学意义(P>0.999)(Fisher确切概率法)。结论肺毛霉病好发于免疫功能低下人群,临床症状、实验室检查、影像学检查缺乏特异性,传统微生物学诊断方法阳性率低,组织病理和宏基因组二代测序有助于提高诊断阳性率,可根据患者情况采取单药治疗、多药联合治疗、手术联合抗真菌药物治疗。

Objective To analyze the clinical data of patients with pulmonary mucormycosis,and to explore the clinical characteristics and diagnosis and treatment protocol of pulmonary mucormycosis.Methods Thirty-three patients with pulmonary mucormycosis were diagnosed and treated in Luohe Central Hospital from January 2021 to April 2023.The clinical data as clinical symptoms,laboratory tests,imaging examinations,etiological diagnosis,treatment protocol and prognosis were recorded.Results Among these 33 patients,the clinical symptoms were fever in 24 patients,cough in33,and hemoptysis in 18.The underlying diseases were diabetes mellitus in 19 patients,solid organ transplantation in 6,blood disease in 5,and chronic kidney disease in 3.One patient had no underlying disease.Twenty-three patients were complicated with viral infection.The C-reactive protein was 48.1(8.5,108.0)mg/L,the erythrocyte sedimentation rate was(57.5±27.9)mm/h,and there were no blood routine,liver function or renal function abnormalities.Chest CT images of these 33 patients were diverse and multiple signs coexisting,with consolidation in 26 patients,cavity in 16,airway stenosis in 15,pleural effusion in 13,mediastinal and hilar lymph node enlargement in 11,pulmonary ground-glass shadow in 4,pulmonary nodule in 2,"reversed halo sign"in 2,and bronchitis in 1;and multiple lobe involvement in 31and single lobe involvement in 2.The positive rate of metagenomic next-generation sequencing in the diagnosis of pulmonary mucormycosis(86.7%)was higher than that of smear microscopy(24.2%),fungal culture(15.2%)and histopathology(50.0%)(χ^(2)=24.649,P<0.001;χ^(2)=32.156,P<0.001;χ^(2)=8.314,P=0.004),was higher of histopathology than that of smear microscopy and fungal culture(χ^(2)=3.873,P=0.049;χ^(2)=7.771,P=0.005),and showed no significant difference between the smear microscopy and fungal culture results(χ^(2)=0.862,P=0.353).Among these 33 patients,25 were treated with antifungal drugs alone,including amphotericin B monotherapy in 2,posaconazole or esaconazole monotherapy in 6,and amphotericin B combined with posaconazole or esaconazole in 17;7were treated with surgery combined with antifungal drugs,including posaconazole monotherapy in 1 and amphotericin B combined with posaconazole in 6;1 abandoned treatment.Among 8 patients receiving monotherapy,7 were improved and discharged,and among 17 patients receiving multi-drug combination therapy,14 were improved and discharged.There was no significant difference in the response rate between monotherapy(87.5%)and multi-drug combination therapy(82.4%)(P>0.999)(Fisher's Exact Test).Among 25 patients receiving antifungal drugs alone,21 were improved and discharged,and 4 died;and among 7 patients treated with surgery combined with antifungal drugs,6 were improved and discharged,and 1 died.There was no significant difference in response rate between antifungal therapy alone(84.0%)and surgery combined with antifungal therapy(85.7%)(P>0.999)(Fisher's Exact Test).Conclusions Pulmonary mucormycosis tends to occur in immunocompromised populations.Clinical symptoms,laboratory tests and imaging examinations lack specificity,and the positive rate of conventional microbiological diagnostic methods is low.Histopathology and metagenomic next-generation sequencing are helpful to improve the diagnostic positive rate.Monotherapy,multi-drug combination therapy,and surgery combined with antifungal drugs can be selected according to the patients'conditions.