| Summary: | Abstract 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.
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