Abstract Background Cryptococcal pleuritis is a rare manifestation of Cryptococcus neoformans infection and typically presents as a lymphocyte-predominant exudative effusion. We describe an uncommon case of C. neoformans repeatedly isolated from a persistent transudative pleural effusion in an HIV-negative patient with end-stage renal disease (ESRD) and diabetes; two conditions known to cause significant secondary immune dysfunction. Case Presentation A 60-year-old woman with ESRD on hemodialysis, heart failure with reduced ejection fraction (20-25%), and poorly controlled diabetes (hemoglobin A1c (A1c) 8.1%) was admitted after an outpatient thoracentesis for a right-sided effusion grew C. neoformans. The fluid was a lymphocyte-predominant (80%) transudate (white blood cell (WBC) 956/µL, protein 1.8 g/dL, lactate dehydrogenase (LDH) 79 IU/L). Repeat thoracentesis 2 weeks later again showed a lymphocyte-predominant (71%) transudate that met Light’s criteria (WBC 589/µL, protein 1.8 g/dL, LDH 90 IU/L; serum protein 6.3 g/dL, LDH 352 IU/L; fluid/serum protein ratio 0.29, fluid/serum LDH ratio 0.26). This fluid again grew C. neoformans. Evaluation for dissemination included negative cerebrospinal fluid (CSF) and bronchoalveolar lavage (BAL) cultures, as well as negative fungal stains from a skin biopsy. Serum cryptococcal antigen was negative (titer 1:5). She was treated with liposomal amphotericin B and flucytosine, followed by long-term fluconazole. Discussion This case supports a proposed “two-hit” mechanism. First, chronic heart failure and ESRD provided the “first hit” of a persistent transudative effusion, which served as a permissive reservoir. Second, uremia and diabetes related immune dysfunction provided the “second hit” by blunting the local inflammatory response, allowing C. neoformans to persist without inducing the expected conversion to an exudate. A comprehensive evaluation for dissemination (including negative CSF cultures, BAL cultures, and skin biopsy fungal stains) combined with a negative serum antigen, strongly indicates an isolated, localized pleural infection. Transudative cryptococcal effusions have been reported only rarely, such as in end-stage liver disease. Conclusion This case challenges the clinical assumption that all pleural infections must produce an exudate and expands awareness of opportunistic infections in the growing population of non-HIV, metabolically immunocompromised hosts. Cryptococcus neoformans can, in rare instances, infect a pre-existing transudative effusion in HIV-negative patients with metabolic immune dysfunction, such as ESRD and diabetes. Fungal cultures should be considered for unexplained or persistent transudates in such high-risk individuals, even in the absence of typical exudative findings. This abstract is funded by: None
Chapagain et al. (Fri,) studied this question.