Cryptococcosis is an opportunistic fungal infection mainly caused by Cryptococcus neoformans and C. gattii , affecting immunocompromised individuals. Diagnosis is based on culture, detection of cryptococcal antigen, or direct visualization. Although rare, the non-encapsulated form of the fungus can be identified, making diagnosis difficult due to the absence of its main virulence factor: the polysaccharide capsule, which has antiphagocytic and immunomodulatory functions. Patient F.B., 35-year-old female, with a recent AIDS diagnosis (CD4: 215 cells/mm³; viral load: 126,000 copies/mL), hospitalized for suspected pulmonary tuberculosis. Presented hypoxemia, elevated lactate dehydrogenase, ground-glass opacities, and increased mediastinal lymph nodes on chest CT. Tests for acid-fast bacilli and rapid molecular testing were negative. Empirical treatment for pneumocystosis was initiated. During the investigation, paired blood cultures revealed Cryptococcus sp. without visible capsule and with negative serum cryptococcal antigen. Cerebrospinal fluid antigen, direct examination, and culture were also negative. Treatment with liposomal amphotericin B and flucytosine was started. After eight days, she developed respiratory failure, required intubation, and died of cardiorespiratory arrest. Autopsy showed pulmonary congestion, alveolar hemorrhage, and early pneumonia, without typical lesions caused by Cryptococcus sp. Cryptococcosis may disseminate hematogenously or via lymphatic spread, generally from a pulmonary focus. The fungal capsule is the main virulence factor, and its absence impairs both immune response and diagnostic accuracy, as seen in this case where conventional tests were negative. Radiologically, infection may present as masses, nodules, or consolidations; histopathologically, as granulomas and giant cells. This case highlights the diagnostic and therapeutic challenges of non-encapsulated Cryptococcus forms, especially in patients with AIDS, and underscores the need for further research into the immunopathogenesis of these variants to reduce the high mortality associated with disseminated cryptococcosis.
Tavares et al. (Sun,) studied this question.