Pleural effusion and Cryptococcus: case series and systematic review of the literature

Abstract Background Cryptococcus neoformans infection occurs more frequently in immunocompromised individuals, with pulmonary and cerebral forms being the most common. Among pulmonary manifestations, pleural effusion in cryptococcosis is an exceptional presentation. Methods We present a series of four cases of cryptococcosis with empyema caused by Cryptococcus neoformans diagnosed at a single centre and we conducted a systematic review of the literature on cases of cryptococcal pleural effusion. 32 were selected for data extraction and analysis. Results The median patient age was 59 years, with 72% over 50 years old. The infection was more common in males (72%). 62% cases were disseminated infection and 34% localized. Cryptococcus neoformans was the most frequent species (90%). Common predisposing factors included cirrhosis (22%), solid organ transplantation (12.5%), and malignancy (19%). HIV infection was infrequent (6%). Pleural effusions were unilateral in 67% of cases and bilateral in 32%. Radiological findings included consolidations (25%), ground-glass opacities, nodules and pleural thickening (15%). Cryptococcal serum antigen was positive in 64% of tested cases, and blood cultures were positive in 57% as well. Lumbar puncture detected Cryptococcus in 7 of 20 cases tested. Microbiological confirmation from pleural fluid was achieved in 75% of cases, with antigen testing aiding diagnosis when cultures were negative. Additional methods included pleural biopsy (positive in 8 cases), bronchoalveolar lavage, EBUS-TBNA, and lung tissue staining. Pleural fluid analysis revealed mostly exudates with lymphocytic predominance (67%). Adenosine deaminase levels were below 35 UI/L in 90% of the tested cases. Glucose and pH values were generally normal. Mortality was documented in 37% of cases. Conclusions Cryptococcal pleural infection is rare and mainly affects immunocompromised, older males, often with disseminated disease. Pleural effusions are typically lymphocyte-predominant and unilateral. Cryptococcal antigen detection in pleural fluid improves diagnosis, especially when cultures fail. Despite treatment, mortality rates remain notably high.