title: Pleural effusion as the initial clinical presentation in disseminated cryptococcosis and fungaemia: an unusual manifestation and a literature review.
abstract: BACKGROUND
  Cryptococcus neoformans infection usually presents as chronic meningitis and is increasingly being recognized in immunocompromised patients. Presentation with pleural effusion is rare in cryptococcal disease; in fact, only 4 cases of pleural effusion as the initial clinical presentation in cryptococcosis have been reported in English-language literature to date. We report the first case of pleural effusion as the initial clinical presentation in a renal transplant recipient who was initially misdiagnosed with tuberculous pleuritis but who then developed fungaemia and disseminated cryptococcosis. The examination of this rare manifestation and the accompanying literature review will contribute to increased recognition of the disease and a reduction in misdiagnoses.
  
  
  METHODS
  We describe a 63-year-old male renal transplant recipient on an immunosuppressive regimen who was admitted for left pleural effusion and fever. Cytological examinations and pleural fluid culture were nonspecific and negative. Thoracoscopy only found chronic, nonspecific inflammation with fibrosis in the pleura. After empirical anti-tuberculous therapy, the patient developed an elevated temperature, a severe headache and vomiting and fainted in the ward. Cryptococci were specifically found in the cerebrospinal fluid following lumbar puncture. Blood cultures were twice positive for C. neoformans one week later. He was transferred to the respiratory intensive care unit (RICU) immediately and was placed on non-invasive ventilation for respiratory failure for 2 days. He developed meningoencephalitis and fungaemia with C. neoformans during hospitalization. He was given amphotericin B liposome combined with 5-flucytosine and voriconazole for first 11 days, then amphotericin B liposome combined with 5-flucytosine sustained to 8 weeks, after that changed to fluconazole for maintenance. His condition improved after antifungal treatment, non-invasive ventilation and other support. Further pathological consultation and periodic acid-Schiff staining revealed Cryptococcus organisms in pleural sections, providing reliable evidence for cryptococcal pleuritis.
  
  
  CONCLUSIONS
  Pleural effusion is an unusual manifestation of cryptococcosis. Cryptococcal infection must be considered in the case of patients on immunosuppressives, especially solid-organ transplant recipients, who present with pleural effusion, even if pleural fluid culture is negative. Close communication between the pathologist and the clinician, multiple special biopsy section stains and careful review are important and may contribute to decreasing misdiagnosis.
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. chenmayun@126.com.
authors.forename: Mayun
authors.initials: M
authors.lastname: Chen
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. 910966090@qq.com.
authors.forename: Xiaomi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. 185819484@qq.com.
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. 851230705@qq.com.
authors.forename: Caijun
authors.initials: C
authors.lastname: Dai
authors.affiliation: Wenzhou Medical University, Wenzhou, China. chendunshun@sina.com.
authors.forename: Dunshun
authors.initials: D
authors.lastname: Chen
authors.affiliation: Division of Radiology Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. wzmcyc@126.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. xuxiaomei248@163.com.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. zdyaodan@163.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Yao
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. taiyang2630@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. wzliyp@163.com.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. wzyxywlx@163.com.
authors.forename: Liangxing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China. zjwzhxy@126.com.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Huang
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use; D003453:Cryptococcosis / Q000150:complications* / Q000175:diagnosis* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000302:isolation & purification; D015725:Fluconazole / Q000627:therapeutic use; D005437:Flucytosine / Q000627:therapeutic use; D016469:Fungemia / Q000150:complications* / Q000175:diagnosis* / Q000382:microbiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000150:complications* / Q000175:diagnosis / Q000382:microbiology; D065819:Voriconazole / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine; D065819:Voriconazole