播散性隐球菌病1例分析

分析在1例肝硬化脾切除术后患者被新型隐球菌侵入血流引起播散性隐球菌病的临床表现、治疗措施与实验室检测结果。患者,男性,30岁,于2016年3月因“脾大、脾功能亢进”行“脾切除+贲门周围血管离断术”,术后多次无明显诱因发热,体温最高39 ℃,相继伴背痛、左下肢脓肿和右髋关节痛。CT和MRI显示患者肺部病变及多处骨质破坏,期间抗生素治疗效果不佳。2017年4月19日对脓液直接革兰染色、墨汁染色,使用API 32C、Vitek 2 Compact、rDNA ITS和IGS序列分析等方法对分离自患者脓液、血液中的菌株进行鉴定,检测患者血清中隐球菌抗原,使用ATB FUNGUS 3进行抗真菌药敏试验。结果在新鲜脓液标本墨汁染色后菌株呈现厚厚的荚膜,从脓液及血液中分离出的菌株经API 32C、Vitek 2 Compact、rDNA ITS和IGS序列分析均鉴定该菌为新型隐球菌,血清新型隐球菌荚膜抗原阳性。该菌对5-氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑及伏立康唑的最小抑菌浓度分别为：<4 mg/L、<0.5 mg/L、4 mg/L、≤0.25 mg/L和0.125 mg/L。给予“氟康唑联合两性霉素B”抗感染治疗2个月脓肿缩小,6个月患者康复。隐球菌感染起病隐匿且临床症状不典型,缺乏特异性,经血流播散造成血流感染会累及包括皮肤、骨骼等全身多个脏器。临床应尽早采血培养监测,去除原发病灶以切断感染途径并进行有效抗隐球菌治疗。     

获得性免疫缺陷综合征合并孤立性肿块型肺隐球菌病或周围型肺癌的CT鉴别诊断

目的:探讨获得性免疫缺陷综合征(AIDS)合并孤立性肿块型肺隐球菌病或周围型肺癌的CT诊断与鉴别诊断。方法:回顾性分析经病理确诊的21例AIDS合并孤立性肿块型肺隐球菌病和14例AIDS合并周围型肺癌患者的胸部CT影像,比较两组患者病灶的分布、大小、内部结构、形态、边缘等。结果:21例孤立性肿块型肺隐球菌病病灶的最大径为(2.03±0.99) cm,显示空洞6例(其中薄壁空洞5例),不规则形6例,分叶征7例、毛刺征4例。14例AIDS合并周围型肺癌患者病灶的最大径为(3.37±2.12) cm,显示磨玻璃影4例,类圆形14例,分叶征12例、毛刺征8例。两组病灶大小、磨玻璃影、空洞、不规则形、分叶征及毛刺征比例差异均有统计学意义(P0.05)。结论:与合并周围型肺癌相比,孤立性肿块型肺隐球菌病病灶多较小,分叶征、毛刺征少见,实性不规则形结节和薄壁空洞较多见;CT检查有助于二者的鉴别诊断。     

An asymptomatic case of pulmonary cryptococcosis with endobronchial polypoid lesions and bilateral infiltrative shadow

A case of pulmonary cryptococcosis with focal endobronchial polypoid lesions is described. A 64-year-old woman consulted our hospital for further evaluation of an abnormal shadow on a chest radiograph. She had been prescribed corticosteroid for rheumatoid arthritis. Chest radiographs revealed an infiltrative shadow in the right lower and left middle and lower lung fields, and chest computed tomography (CT) revealed bilateral airspace consolidations and multiple nodules. A bronchoscopic finding revealed white polypoid lesions at the orifice of the posterior basal bronchus in the left lower lobe. Histopathological examination of transbronchial biopsy specimens demonstrated cryptococcal organisms. After fluconazole therapy for 4 months, the infiltrate had decreased in size and the bronchial polypoid lesions had disappeared.     

Prevention of cryptococcosis in HIV-infected patients with limited access to highly active antiretroviral therapy: evidence for primary azole prophylaxis

Despite advances in the treatment of HIV disease, the incidence and mortality of invasive cryptococcal disease remain significant. A matched, case-control study was performed to examine the impact of highly active antiretroviral therapy (HAART) and azole use on the incidence of invasive cryptococcal disease in HIV-infected patients. The study was performed at a metropolitan hospital with a large indigent population and an incidence of seven cases of cryptococcal disease per 1000 persons with AIDS. Bivariate analysis, matched on CD4 count, revealed that both HAART use [odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.99] and azole use (OR 0.14; 95% CI 0.06-0.34) had a protective effect. Conditional logistic regression stratified on CD4 lymphocyte count revealed a protective role for azole use (OR 0.15; 95% CI 0.06-0.40) but not for HAART use (OR 0.47; 95% CI 0.18-1.26). Of note, the prevalence of HAART use was low in both cases and controls, with only 12% of cases and 23% of controls on HAART. The results of this study support previous evidence that azole use prevents invasive cryptococcal disease. Although current guidelines for the prophylaxis of opportunistic infections do not suggest routine prophylaxis for cryptococcal infection, this issue should be reconsidered, especially in populations that have a low prevalence of HAART use.     

Asymptomatic pulmonary cryptococcosis in solid organ transplantation: report of four cases and review of the literature

Abstract: Cryptococcus neoformans is the third most common cause of invasive fungal infections in solid organ transplantation. The infection generally presents as disseminated disease, involving multiple sites including the central nervous system, lungs, and skin. An increase in the incidence of primary pulmonary cryptococcal infections has been reported recently in solid organ recipients; these infections were generally symptomatic with an accelerated clinical course. We report four cases of asymptomatic pulmonary cryptococcosis in solid organ recipients (kidney, n=2, heart, n=2). In each case, an incidental finding on a routine chest radiograph led to the microbiological or histopathological diagnosis of invasive pulmonary C. neoformans infection. In these patients, cryptococcosis occurred a median of 25 months (range 7–36 months) after organ transplantation. All patients had a calcineurin inhibitor, prednisone, and azathioprine or mycophenolate mofetil as part of their immunosuppressive therapy at the time of diagnosis. Serum cryptococcal antigen was available and positive in the three patients studied; assessment of cerebrospinal fluid (CSF) of all four patients revealed no organisms by smear or culture. Therapy consisted of oral fluconazole in all cases, with flucytosine in one case, combined with resection of lung tissue in two individuals. All patients have remained free of cryptococcal disease (follow‐up median 42 months, from 18 to 88 months). Cryptococcal disease in solid organ recipients may present as asymptomatic, localized pulmonary disease. The natural history of such infections is unknown. New pulmonary radiographic findings should prompt an aggressive diagnostic evaluation including serum and CSF cryptococcal antigen assays, and a biopsy of pulmonary lesions. Prolonged therapy may be used to reduce the risk of progression and dissemination during periods of intensified immune suppression.     

非免疫缺陷患者肺隐球菌病的临床特征及疗效分析

目的分析非免疫缺陷患者肺隐球菌病的临床特征及疗效。 方法回顾性分析陆军特色医学中心2017年1月至2020年6月确诊肺隐球菌病患者的病历资料39例,人口学资料,基础疾病,临床表现,影像学特征,病理检查结果,治疗方案和临床结局。收集患者肺组织病理学检测结果和痰液样本,分析是否存在隐球菌感染,对部分患者进行了隐球菌抗原检测,进行分析总结。 结果39例患者,男21例,女18例。20例(51.28%)体检发现肺部结节,19例(48.72%)有咳嗽、咳痰、发热临床症状,39例患者均确诊肺隐球菌病。32例(82.05%)行手术切除病变肺组织后辅助于抗真菌治疗药物,手术切除肺组织均行病理检查确诊隐球菌感染;7例(17.95%)单纯抗真菌药物治疗者中,有3例行肺穿刺活检证实肺隐球菌,1例血清隐球菌荚膜多糖抗原测试呈阳性,1例痰液培养提示肺隐球菌,2例肺泡灌洗液检出隐球菌。随访中发现手术切除联合抗真菌治疗相比单纯药物抗真菌治疗者,疗程短。 结论非免疫缺陷肺隐球菌病患者的临床表现无特异性,检测血清或呼吸道标本中的隐球菌抗原或肺组织活检是确诊隐球菌感染的诊断手段。手术联合抗真菌药物是治疗隐球菌肺病的有效方法。     

Middle cerebral artery territory infarct due to Cryptococcus infectionstitle

Cryptococcal meningitis is the most common manifestation of cryptococcosis and is caused by the encapsulated yeast organism Cryptococcus neoformans. It occurs most commonly in patients with impaired cell‐mediated immunity such as in HIV infection; patients with hematological malignancies; patients post solid‐organ transplantation; on chronic steroids or immunosuppressants. Clinically, stroke can arise as a complication of cryptococcal meningitis. While cerebrospinal fluid (CSF) examination is usually not indicated for evaluation of stroke patients, demonstration of cryptococcal yeast forms in CSF is valuable in guiding appropriate therapy in arterial stroke caused by Cryptococci. Herein, we describe the CSF and radiologic correlation in a female patient who presented with disseminated cryptococcosis, cryptococcal meninigitis and a middle cerebral artery infarct. Diagn. Cytopathol. 2015;43:632–634. © 2014 Wiley Periodicals, Inc.     

肝移植术后原发性肺隐球菌病3例临床分析

目的探讨原位肝移植术后原发性肺隐球菌病(PPC)的诊断和治疗。方法收集武警总医院2005年4月～2009年12月1302例原位肝移植术后3例并发PPC患者的临床资料,结合相关文献进行复习。结果 3例患者分别在肝移植术后6、13、31个月并发PPC;肺穿刺活组织病理学检查确诊1例,临床诊断2例(乳胶凝集试验阳性及CT检查肺部阴影);均采用单药治疗,氟康唑治疗1例,伊曲康唑治疗2例,均未出现药物相关不良反应。结论 PPC多发生在肝移植术后中、远期,缺乏特征性临床表现和影像学特征,肺穿刺活组织学检查是PPC的确诊手段,唑类抗真菌药对PPC有效且无明显不良反应。     

Detection of CD4(+) T-cell antibodies in a patient with idiopathic CD4 T lymphocytopenia and cryptococcal meningitis

Idiopathic CD4(+) T lymphocytopenia (ICL) is defined as a CD4(+) T-cell count <0.3 x 10(9)/l or <20% of the total T-cell count on two occasions in the absence of any immunodeficiency disorder or therapy associated with reduced CD4(+) T-cell count. Although several mechanisms of ICL have been reported, the pathophysiology is still largely unknown. This case report describes a patient who presented with cryptococcal meningitis and was subsequently discovered to meet the criteria for ICL. Flow cytometric analysis of the patient's peripheral blood mononuclear cells revealed antibodies coating a much larger proportion of his CD4(+) T cells (33.61%) than the CD4(+) T cells of normal donors (3.94 +/- 1.77%). The reasons behind the development of these autoantibodies are explored.