Figure 1 - available from: BMC Infectious Diseases
This content is subject to copyright. Terms and conditions apply.
Chest CT (2014.6.3) showed a left-sided pleural effusion with compressive atelectasis of the left lower lobe (a, b), multiple nodules scattered in both lungs (c), and calcification in the nodules in the left upper lobe (d). Chest CT (2014.9.26) revealed that the left pleural effusion was completely resolved (e, f), but multiple nodules and calcification were still present (g, h)
Source publication
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-l...
Contexts in source publication
Context 1
... of 38.5 °C and decreased breath sounds at the left base with dull- ness on percussion. A chest computed tomography (CT) scan showed left-sided pleural effusion, along with com- pressive atelectasis of the left lower lobe and scattered multiple nodules on both sides, and calcification was ob- served in the nodules in the left upper lobe (Fig. ...
Context 2
... days, then amphotericin B liposome combined with 5-flucytosine sustained to 8 weeks, which was then changed to flucona- zole for maintenance. The left pleural effusion no longer accumulated, and the fever, headache and dry cough subsided. The patient improved and became asymptom- atic three weeks after the antifungal therapy. A follow-up chest CT (Fig. 1e-h) revealed resolution of the ...
Similar publications
In the present study 225 pigeon droppings from two districts of West Bengal (Kolkata
and North 24 Parganas) were collected. In total 24 (10.67%) Cryptococcus
neoformans isolates were confirmed by phenotypical and biochemical characteristics.
Minimum inhibitory concentration of the isolates was done by agar diffusion assay
against fluconazole, ketoc...
Citations
... Isolated pleural effusion has rarely been reported as the initial clinical presentation in opportunistic cryptococcal infection. 1,2 In an era marked by a growing number of immunosuppressed patients, it is crucial to consider opportunistic infections as an alternative cause for early diagnosis and treatment in immunocompromised patients with pleural effusion of unknown origin. After the measurement of pleural fluid adenosine deaminase (ADA) levels became common in the 1990s, a few cases of cryptococcal pleural effusion reported their pleural fluid ADA levels, and elevated ADA levels have often been reported among these cases. ...
... After the measurement of pleural fluid adenosine deaminase (ADA) levels became common in the 1990s, a few cases of cryptococcal pleural effusion reported their pleural fluid ADA levels, and elevated ADA levels have often been reported among these cases. [2][3][4][5][6][7] These characteristics of cryptococcal pleural effusion pose challenges in differentiating it from tuberculous pleural effusion (TPE), especially in regions with a high to intermediate tuberculosis prevalence. Some prior cases of cryptococcal pleural effusion have resulted in unnecessary anti-tuberculosis therapy. ...
Isolated cryptococcal pleural effusion is rare as the initial clinical presentation in opportunistic cryptococcal infection. We describe a 59‐year‐old male heart transplantation recipient who presented with a mononuclear‐leukocyte‐predominant exudative pleural effusion, with adenosine deaminase levels (ADA) of 37 IU/L and focal pleural nodularity on computed tomography. A thorough evaluation, including pleural fluid culture, cryptococcal antigen, and histological examination, led to the diagnosis of cryptococcal pleural effusion. Antifungal therapy with fluconazole of 400 mg/day showed clinical and radiological improvement. A literature review identified six cases of cryptococcal pleural effusion that reported pleural fluid ADA levels. All cases, including the present one, involved immunocompromised hosts and exhibited a mononuclear‐leukocyte‐predominant exudate. High pleural fluid ADA levels were observed in approximately half of these cases. The pleural fluid cryptococcal antigen test was an important diagnostic tool for early diagnosis. In an era where immunocompromised hosts are increasing, cryptococcal infection should be considered as a potential aetiology in immunosuppressed patients with an exudative pleural effusion of unknown cause, even if ADA levels are elevated.
... Some reports describe an exudative effusion with a predominance of lymphocytes and detection of C. neoformans via either pleural fluid culture or antigen detection (Longhitano et al., 2022). However, low pathogen numbers within pleural effusion samples may result in negative culture detection, and the pleural effusion may be nonspecific (Chen et al., 2015). Therefore, it is easy to delay the diagnosis when the patient starts with isolated pleural effusion, especially when the patient has concurrent tumor, which was misdiagnosed as malignant pleural effusion. ...
Objective
The aim of this study is to report an isolated pleural cryptococcosis with pleural effusion as the only manifestation, confirmed by pleural biopsy in a patient with thymoma combined with myasthenia gravis, who developed pleural effusion of unknown origin after long-term glucocorticoids and tacrolimus therapy.
Methods
Pathological examination of the right pleural biopsy tissue from a patient with unexplained recurrent pleural effusion was implemented. Morphological analysis of the fungal component and metagenomic next-generation sequencing (mNGS) on the pleural tissue were performed.
Results
A biopsy specimen of the right pleura revealed numerous yeast-like organisms surrounded by mucous capsules and Cryptococcus neoformans was detected by mNGS with a species-specific read number (SSRN) of 4, confirming the diagnosis of pleural cryptococcosis. Pleural effusion was eliminated with amphotericin B and fluconazole, and healthy status was maintained at the time of review 1 year later.
Conclusion
Cryptococcosis, manifested by simple pleural effusion, is extremely rare, but when repeated pleural effusion occurs in immunocompromised patients or in patients with malignant tumors, the possibility of cryptococcosis should be treated with high vigilance and pleural biopsy is recommended if necessary in order to confirm the diagnosis.
... The detection rates of Cryptococcus neoformans with Gomori-methenamine silver stain and periodic acid-Schiff stain are 100%. The morphology present in tissue with Cryptococcus neoformans infection using Gomori-methenamine silver and periodic acid-Schiff (PAS) staining reveals arrow-based budding yeasts (4-10 μm) with a thick capsule, while the morphology present in tissue with histoplasmosis reveals small yeasts (2-4 μm) with narrow-based budding grouped in clusters inside macrophages [14]. ...
Pleural involvement of cryptococcal infection is uncommon and is more commonly observed in immunocompromised hosts than in immunocompetent ones. Pleural involvement in cryptococcal infections can manifest with or without pleural effusion. The presence of Cryptococcus spp. in the effusion or pleura is required for the diagnosis of cryptococcal pleural infection, which is commonly determined by pleural biopsy, fluid culture, and/or detection of cryptococcal antigen in the pleura or pleural fluid.
... Fungi are uncommon in pleural infections representing 3% of cases, mostly corresponding to Candida species [18]. Pleural effusion as a manifestation of cryptococcosis is extremely rare but should be suspected in immunocompromised patients; since pleural effusion cultures for Cryptococcus are usually negative, probably due to the small number of fungi in the pleural fluid, pathologists should keep this suspicion high when examining immunocompromised patients' pleural biopsies to avoid overlooking it, and colorations such as Methemenamine Silver and PAS could help in the diagnosis [23]. It is postulated that the release of antigens, rather than the fungus itself, is responsible for pleural effusion, thus, cryptococcal antigens can be detected in the pleural fluid, similarly to the blood and cerebrospinal fluid [23]. ...
... Pleural effusion as a manifestation of cryptococcosis is extremely rare but should be suspected in immunocompromised patients; since pleural effusion cultures for Cryptococcus are usually negative, probably due to the small number of fungi in the pleural fluid, pathologists should keep this suspicion high when examining immunocompromised patients' pleural biopsies to avoid overlooking it, and colorations such as Methemenamine Silver and PAS could help in the diagnosis [23]. It is postulated that the release of antigens, rather than the fungus itself, is responsible for pleural effusion, thus, cryptococcal antigens can be detected in the pleural fluid, similarly to the blood and cerebrospinal fluid [23]. Viral pneumonias can be also associated with pleural effusions with non-COVID-19 pneumonias showing pleural effusion in 25% of the cases compared to 3% of COVID-19 pneumonias [24], attributed often to comorbidities or directly to the viral infection [25]. ...
Simple Summary
The pleura is a cavity whose pathology ranges from simple fluid accumulation to tumor development, all inducing important consequences in patents health, and usually having an important association with local inflammation. Understanding the pathophysiology of pleural inflammation helps the development of the correct treatment strategies and opens new windows in pleural research. Thus, the aim of this review is to present the etiologies and the pathophysiological mechanisms of pleural inflammation with a special interest in their role on tumor development and diagnosis.
Abstract
Pleural effusions are a common respiratory condition with many etiologies. Nonmalignant etiologies explain most pleural effusions and despite being nonmalignant, they can be associated with poor survival; thus, it is important to understand their pathophysiology. Furthermore, diagnosing a benign pleural pathology always harbors the uncertainty of a false-negative diagnosis for physicians and pathologists, especially for the group of non-specific pleuritis. This review aims to present the role of the inflammation in the development of benign pleural effusions, with a special interest in their pathophysiology and their association with malignancy.
... The presence of either of these conditions demands an aggressive treatment regimen with amphotericin B and flucytosine, while milder infections, such as pulmonary Cryptococcosis, can be adequately managed with fluconazole [5]. Cryptococcal infection in the lungs usually causes an exudative effusion [6][7][8]. In our literature review, we have not found a case of an individual with a transudative effusion who had Cryptococcal pneumonia or Cryptococcal pleural infection. ...
... An immunodeficient state associated with Cryptococcus is liver cirrhosis, which was the likely risk factor of our patient. There are various Cryptococcal presentations in cirrhotic patients, including meningitis, pneumonia, peritonitis, pleuritis, and disseminated infection [7,8,[11][12][13][14][15]. We present a case of disseminated Cryptococcus infection who initially presented with a transudative pleural effusion that was antigen-positive and culture-positive for C. neoformans. ...
To our knowledge, this is the first case report of a transudative pleural effusion with positive Cryptococcal antigen and culture. We describe a 32-year-old male with end-stage liver disease (ESLD) who presented to an outside hospital with dyspnea and a large pleural effusion. An initial pleural fluid analysis was positive for Cryptococcal Ag. However, the infection was eventually found to be widespread as he had positive Cryptococcal Ag and cultures in his pleural fluid, serum, and cerebrospinal fluid (CSF). His antimicrobial regiment was escalated from fluconazole to amphotericin B and flucytosine. His medical condition deteriorated, and the patient passed away. Due to its rarity and range of clinical severity, diagnosis of disseminated Cryptococcosis can be delayed. We present this case to bring awareness of this diagnosis as a differential in immunocompromised patients regardless of a transudative pleural effusion.
... Candida species are responsible for the most of the cases with high rates of mortality [8,9]. Additionally, Cryptococcus neoformans [10], Aspergillus species [11][12][13][14][15][16], Trichosporon and Fusarium species [17] have been described as rare causes of pleural effusion is some case reports. ...
Trichoderma longibrachiatum is a fungus belonging to the genus Trichoderma. Trichoderma longibrachiatum is not thought as a pathogenic for healthy individuals. However, it has the ability to produce toxic peptides and extracellular proteases and has been described to cause invasive infections in immunocompromised hosts. Trichoderma longibrachiatum has been reported as the causative microorganism of lung infections, skin infections, sinus infections, otitis, stomatitis endocarditis, pericarditis, gastrointestinal infections, mediastinitis and peritonitis. We report the first case of pneumonia with parapneumonic effusion in an old woman with diabetes mellitus due to Trichoderma longibrachiatum.
... 14 Pleural effusion is a rare imaging manifestation associated with cryptococcosis. Patients with meningitis and compromised immunity are prone to develop pleural effusion, 18 and cryptococcal antigens may stimulate the pleura to produce pleural effusion. 19 Statistical analysis in our study showed that patients with cavitation were more prone to have CNS involvement. ...
Objective
This study aimed to compare the clinical features of pulmonary cryptococcosis (PC) in patients with and without central nervous system (CNS) involvement.
Methods
We retrospectively reviewed demographics, presenting symptoms, radiographic features, and laboratory findings of patients diagnosed with PC in 28 hospitals from 2010 to 2019. Risk factors for CNS involvement were analyzed using logistic regression models.
Result
A total of 440 patients were included, and 36 (8.2%) had CNS involvement. Significant differences in fever, headache, and chills occurred between the two groups (overall and with/without CNS involvement) for fever (17.8% [78/440]; 52.8% vs. 14.6% of patients, respectively), headache (4.5% [20/440]; 55.6% vs. 0% of patients, respectively), and chills (4.3% [19/440]; 13.9% vs. 3.5% of patients, respectively). The common imaging manifestation was nodules (66.4%). Multivariate analysis showed that cavitation (adjusted odds ratio [AOR] = 3.552), fever (AOR = 4.182), and headache were risk factors for CNS involvement. Routine blood tests showed no differences between the groups, whereas in cerebrospinal fluid the white blood cell count increased significantly and glucose decreased significantly.
Conclusion
In patients with PC, the risk of CNS involvement increases in patients with headache, fever, and cavitation; these unique clinical features may be helpful in the diagnosis.
... The pattern of granulomas and its role in host-pathogen interactions, particularly in renal post-transplant recipients with cryptococcosis, have been poorly investigated. In general, the histopathological studies published so far have addressed tissue histopathological findings without clear characterization of the granulomatous inflammatory response and its correlation with clinical outcome (Bhowmik et al. 2008;Baer et al. 2009;Chen et al. 2015). ...
Cryptococcosis is the second most common invasive fungal infection reported in renal transplant recipients. Tissue granulomatous inflammation is necessary to contain Cryptococcus infection. This study aims to analyze the granuloma patterns and in situ expression of regulatory T (Treg) immune response in tissue samples from 12 renal transplant recipients with cryptococcosis. Fungal isolates were molecularly identified as Cryptococcus neoformans species complex. A detailed characterization of granulomas in tissue samples from 12 kidney transplant recipients with cryptococcosis was described by checking six lung and six skin biopsies by conventional histology and for immunohistochemical detection of CD4 and Treg markers: forkhead box P3 (FoxP3), interleukin (IL)-10 and transforming-growth factor (TGF)-β. Granulomas were classified as compact, loose or mixed. Patients with mixed (n = 4) and compact (n = 3) granulomatous inflammation patterns were associated with a better prognosis and presented a higher number of CD4+FoxP3+T cells compared to the group of patients with loose granulomas. In counterpart, three out of five patients with loose granulomas died with cryptococcosis. We suggest that Treg may have a protective role in the tissue response to Cryptococcus infection given its association with compact and mixed granulomas in patients with better clinical outcomes.
... The organism may mainly invades lungs and CNS, but also can invade skin, bones and other parts of the body, which is closely related to the patient's immune status [3,11]. With a declining incidence of AIDS-related cryptococcosis in the highly active antiretroviral therapy (HAART) era and with increasing use of immunosuppresants worldwide, HIVnegative individuals may become the predominant group affected by cryptococcosis [10][11][12][13]. Currently, pulmonary cryptococcosis ranked as the third most common pulmonary fungal infection in China, and previous studies have shown that most of the patients with [14][15][16]. ...
Background:
Pulmonary Cryptococcosis is a common fungal infection mainly caused by Cryptococcus neoformans/C.gattii species in immunocompromised patients. Cases of pulmonary cryptococcosis in patients with normal immune function are increasingly common in China. Clinical and radiographic features of pulmonary cryptococcosis are various and without obvious characteristics, so it is often misdiagnosed as pulmonary metastatic tumor or tuberculosis. When coexisting with malignant lung tumors, it was more difficult to differentiate from metastatic lung cancer, although the coexistence of pulmonary cryptococcosis and central type lung cancer is rare. Reviewing the imaging manifestations and diagnosis of the case and the relevant literature will contribute to recognition of the disease and a decrease in misdiagnoses.
Case presentation:
A 72-year-old immunocompetent Han Chinese man had repeated dry cough for more than half a year. CT examination of chest showed an irregular mass at the left hilum of the lung, and two small nodules in the right lung, which were considered as the left central lung cancer with right lung metastasis. However, the patient was diagnosed with pulmonary cryptococcosis coexisting with central type lung cancer based on the results of laboratory examination, percutaneous lung biopsy, fiberoptic bronchoscopy, and surgical pathology. The patient underwent surgical resection of the left central type lung cancer and was placed on fluconazole treatment after a positive diagnosis was made. Five years after the lung cancer surgery, the patient had a recurrence, but the pulmonary cryptococcus nodule disappeared.
Conclusion:
Our case shows that CT findings of central type lung cancer with multiple pulmonary nodules are not necessarily metastases, but may be coexisting pulmonary cryptococcosis. CT images of cryptococcosis of the lung were diverse and have no obvious characteristics, so it was very difficult to distinguish from metastatic tumors. CT-guided percutaneous lung biopsy was a simple and efficient method for identification.
... According to a previous review from China [8], the incidence of cryptococcosis in KT recipients was estimated to be 0.76% in China. However, few cases of cryptococcosis in patients who have undergone KT have been reported in China [9][10][11]. erefore, the characteristics of cryptococcosis in KT recipients in China are not well defined. ...
... However, opportunistic infections, including invasive fungal or viral infections and tuberculosis, remain a concern in patients who have undergone KT in terms of successful longterm outcomes [1,13]. Only a small number of cases of post-KT cryptococcosis have been reported in mainland China [9][10][11]. In the present study, 37 patients diagnosed with post-KT cryptococcosis and their characteristics were analyzed. ...
Background:
Cryptococcosis following kidney transplantation (KT) is rare but is associated with considerably increased risk of mortality. At present, data on the association between cryptococcosis and KT in mainland China remain relatively limited.
Objectives:
This study aims to review our experience related to the management of cryptococcosis following KT at a Chinese tertiary hospital.
Methods:
All patients with cryptococcosis following KT admitted to our hospital from January 2010 to December 2018 were reviewed.
Results:
A total of 37 patients with cryptococcosis were enrolled (males: 62.2%). The mean age of the patients was 49.5 ± 9.38 (20-64) years. The average time to infection following KT was 7.0 ± 5.50 years (5 months to 21 years), and 30 patients (81.1%) had cryptococcosis onset >2 years following transplantation. The most common site of infection was the central nervous system, followed by the pulmonary system and skin. Most patients received fluconazole or voriconazole with or without flucytosine as their initial treatment regimen at our hospital. The 2-week mortality rate was 8.1% (3/37), and five patients (13.5%) died within 6 months of being diagnosed with cryptococcosis. Remarkably, all patients who received high-dose fluconazole (800 mg daily) or voriconazole ± flucytosine survived.
Conclusions:
Cryptococcosis in kidney transplant recipients is typically a late-occurring infection, with most patients having cryptococcosis onset >2 years following KT at our hospital. The central nervous system, pulmonary system, and skin are the main sites of infection. Voriconazole or high-dose fluconazole can be used as an alternative therapy for post-KT cryptococcosis.
