A 35-year-old heterosexual man had reduced dexterity in his right hand and difficulty writing; examination revealed right hand incoordination and reduced dexterity. Eight years ago he had had disseminated histoplasmosis, without central nervous system (CNS) involvement, that was successfully treated with 8 months of itraconazole. Brain magnetic resonance imaging revealed right cerebellar and frontal lobe rim-enhancing lesions with central lucency (Figure 1A). The cerebellar lesion was surgically resected. Pathologic examination revealed granulomas and yeast forms (Figures 2A and 2B) and a fungal culture was positive for Histoplasma capsulatum. The patient was also found to have liver and bone marrow involvement consistent with disseminated histoplasmosis. His Histoplasma urine antigen level was 6.15 U (normal, < 1.0 U). He had mild neutropenia; the absolute granulocyte count was 1.53 K/μL (reference range, 1.6-9.8 K/μL). He had a low CD4 cell count of 242 cells/μL (reference range, > 550 cells/μL), but his human immunodeficiency virus antibody test results were negative. The immunoglobulin M (IgM) level was elevated at 377 mg/dL (reference range, 50-200 mg/dL), with a reduced IgG level of 544 mg/dL (reference range, 750-1400 mg/dL) and an IgA level of 74 mg/dL (reference range, 75-310 mg/dL). Genetic testing for X-linked hyper-IgM syndrome was negative. He began treatment with itraconazole, but developed fever and hepatitis. Voriconazole treatment was started at 400 mg/d with clinical and radiological improvement (Figure 1B). Voriconazole trough levels in the serum and cerebrospinal fluid were within therapeutic range.
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A and B, T1-weighted post-gadolinium images before treatment, revealing abscess in right frontal lobe and cerebellum. C and D, T1-weighted post-gadolinium images 14 months after surgical resection of cerebellar lesion and treatment with oral voriconazole.
A, Low-power view of hematoxylin-eosin stain of cerebellar tissue, demonstrating central necrosis (arrow) and surrounding granulomatous changes. B, Higher-power view of hematoxylin-eosin stain, demonstrating small intracellular yeast forms within a macrophage (arrow), with surrounding granulomatous infiltrate. C, Yeast cells of Histoplasma capsulatum (arrow) stained with methenamine silver.
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