A 26-year-old cisgender man with a recent HIV diagnosis and CD4 count of 29 cells/mm³ had started antiretroviral therapy (TDF/3TC and DTG) one month prior to admission to an intensive care unit in Rio de Janeiro. He reported progressive dyspnea for two weeks, cough, daily fever, weight loss, and asthenia, denying headache. Physical examination revealed sarcopenia, tachypnea, and hepatosplenomegaly, with no neurological abnormalities. Laboratory tests showed pancytopenia and dialysis-requiring acute kidney injury. Infectious screening at admission revealed negative serum LF-CrAg, negative urinary antigen for H. capsulatum, and negative urinary lipoarabinomannan. Chest CT showed an atelectatic band and pleural thickening in the right lower lobe; cranial CT was unremarkable. Blood cultures, bone marrow aspirate, and biopsy were collected, and empirical liposomal amphotericin B was initiated. Six days later, both cultures grew Cryptococcus neoformans, sensitive to amphotericin B. Lumbar puncture revealed an opening pressure of 35 cmH₂O and cerebrospinal fluid with reactive qualitative LF-CrAg, 1 cell, protein 50 mg/dL, normal glucose, and positive culture for C. neoformans. Flucytosine was added for cryptococcal meningitis. Bone marrow histopathology showed chronic granulomatous inflammation and Cryptococcus sp. highlighted by Alcian Blue and mucicarmine staining. The admission serum sample was retested after dilution for LF-CrAg and became reactive, confirming a post-zone effect due to antigen excess. Serology for H. capsulatum (Western blot) was reactive for H and M bands, raising the possibility of coinfection. Induction therapy was extended to 41 days due to persistent positive CSF cultures, reflecting the high initial fungal burden. Due to worsening pancytopenia, human immunoglobulin was administered for hemophagocytic lymphohistiocytosis. The patient was discharged 44 days after admission on fluconazole 750 mg/day for consolidation and remains under outpatient follow-up without mycological relapse to date (6 months). In individuals with severe immunosuppression, we emphasize the diagnostic relevance of pairing a nonreactive serum LF-CrAg with fungal blood cultures and/or diluted serum samples, considering the possibility of a post-zone effect. The possibility of coinfection with Cryptococcus spp. and H. capsulatum should be investigated by combining mycological methods, histopathology, serology, and/or molecular biology, as it poses challenges during the consolidation phase of treatment.
Classmann et al. (2026) studied this question.